A reference human induced pluripotent stem cell line for large-scale collaborative studies

Caroline B. Pantazis; Andrian Yang; Erika Lara; Justin A. McDonough; Cornelis Blauwendraat; Lirong Peng; Hideyuki Oguro; Jitendra Kanaujiya; Jizhong Zou; David Sebesta; Gretchen Pratt; Erin Cross; Jeffrey Blockwick; Philip Buxton; Lauren Kinner-Bibeau; Constance Medura; Christopher Tompkins; Stephen Hughes; Marianita Santiana; Faraz Faghri; Mike A. Nalls; Daniel Vitale; Shannon Ballard; Yue A. Qi; Daniel M. Ramos; Kailyn M. Anderson; Julia Stadler; Priyanka Narayan; Jason Papademetriou; Luke Reilly; Matthew P. Nelson; Sanya Aggarwal; Leah U. Rosen; Peter Kirwan; Venkat Pisupati; Steven L. Coon; Sonja W. Scholz; Theresa Priebe; Miriam Öttl; Jian Dong; Marieke Meijer; Lara J.M. Janssen; Vanessa S. Lourenco; Rik van der Kant; Dennis Crusius; Dominik Paquet; Ana Caroline Raulin; Guojun Bu; Aaron Held; Brian J. Wainger; Rebecca M.C. Gabriele; Jackie M. Casey; Selina Wray; Dad Abu-Bonsrah; Clare L. Parish; Melinda S. Beccari; Don W. Cleveland; Emmy Li; Indigo V.L. Rose; Martin Kampmann; Carles Calatayud Aristoy; Patrik Verstreken; Laurin Heinrich; Max Y. Chen; Birgitt Schüle; Dan Dou; Erika L.F. Holzbaur; Maria Clara Zanellati; Richa Basundra; Mohanish Deshmukh; Sarah Cohen; Richa Khanna; Malavika Raman; Zachary S. Nevin; Madeline Matia; Jonas Van Lent; Vincent Timmerman; Bruce R. Conklin; Katherine Johnson Chase; Ke Zhang; Salome Funes; Daryl A. Bosco; Lena Erlebach; Marc Welzer; Deborah Kronenberg-Versteeg; Guochang Lyu; Ernest Arenas; Elena Coccia; Lily Sarrafha; Tim Ahfeldt; John C. Marioni; William C. Skarnes; Mark R. Cookson; Michael E. Ward; Florian T. Merkle

doi:10.1016/j.stem.2022.11.004

A reference human induced pluripotent stem cell line for large-scale collaborative studies

Caroline B. Pantazis, Andrian Yang, Erika Lara, Justin A. McDonough, Cornelis Blauwendraat, Lirong Peng, Hideyuki Oguro, Jitendra Kanaujiya, Jizhong Zou, David Sebesta, Gretchen Pratt, Erin Cross, Jeffrey Blockwick, Philip Buxton, Lauren Kinner-Bibeau, Constance Medura, Christopher Tompkins, Stephen Hughes, Marianita Santiana, Faraz FaghriMike A. Nalls, Daniel Vitale, Shannon Ballard, Yue A. Qi, Daniel M. Ramos, Kailyn M. Anderson, Julia Stadler, Priyanka Narayan, Jason Papademetriou, Luke Reilly, Matthew P. Nelson, Sanya Aggarwal, Leah U. Rosen, Peter Kirwan, Venkat Pisupati, Steven L. Coon, Sonja W. Scholz, Theresa Priebe, Miriam Öttl, Jian Dong, Marieke Meijer, Lara J.M. Janssen, Vanessa S. Lourenco, Rik van der Kant, Dennis Crusius, Dominik Paquet, Ana Caroline Raulin, Guojun Bu, Aaron Held, Brian J. Wainger, Rebecca M.C. Gabriele, Jackie M. Casey, Selina Wray, Dad Abu-Bonsrah, Clare L. Parish, Melinda S. Beccari, Don W. Cleveland, Emmy Li, Indigo V.L. Rose, Martin Kampmann, Carles Calatayud Aristoy, Patrik Verstreken, Laurin Heinrich, Max Y. Chen, Birgitt Schüle, Dan Dou, Erika L.F. Holzbaur, Maria Clara Zanellati, Richa Basundra, Mohanish Deshmukh, Sarah Cohen, Richa Khanna, Malavika Raman, Zachary S. Nevin, Madeline Matia, Jonas Van Lent, Vincent Timmerman, Bruce R. Conklin, Katherine Johnson Chase, Ke Zhang, Salome Funes, Daryl A. Bosco, Lena Erlebach, Marc Welzer, Deborah Kronenberg-Versteeg, Guochang Lyu, Ernest Arenas, Elena Coccia, Lily Sarrafha, Tim Ahfeldt, John C. Marioni, William C. Skarnes, Mark R. Cookson, Michael E. Ward, Florian T. Merkle

Research output: Contribution to journal › Article › peer-review

Abstract

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

Original language	English (US)
Pages (from-to)	1685-1702.e22
Journal	Cell Stem Cell
Volume	29
Issue number	12
DOIs	https://doi.org/10.1016/j.stem.2022.11.004
State	Published - Dec 1 2022

Keywords

CRISPR
differentiation
iPSC
karyotype
p53
pluripotent
reference
single-cell
stem cell
whole-genome

ASJC Scopus subject areas

Molecular Medicine
Genetics
Cell Biology

Access to Document

10.1016/j.stem.2022.11.004

Cite this

Pantazis, C. B., Yang, A., Lara, E., McDonough, J. A., Blauwendraat, C., Peng, L., Oguro, H., Kanaujiya, J., Zou, J., Sebesta, D., Pratt, G., Cross, E., Blockwick, J., Buxton, P., Kinner-Bibeau, L., Medura, C., Tompkins, C., Hughes, S., Santiana, M., ... Merkle, F. T. (2022). A reference human induced pluripotent stem cell line for large-scale collaborative studies. Cell Stem Cell, 29(12), 1685-1702.e22. https://doi.org/10.1016/j.stem.2022.11.004

Pantazis, CB, Yang, A, Lara, E, McDonough, JA, Blauwendraat, C, Peng, L, Oguro, H, Kanaujiya, J, Zou, J, Sebesta, D, Pratt, G, Cross, E, Blockwick, J, Buxton, P, Kinner-Bibeau, L, Medura, C, Tompkins, C, Hughes, S, Santiana, M, Faghri, F, Nalls, MA, Vitale, D, Ballard, S, Qi, YA, Ramos, DM, Anderson, KM, Stadler, J, Narayan, P, Papademetriou, J, Reilly, L, Nelson, MP, Aggarwal, S, Rosen, LU, Kirwan, P, Pisupati, V, Coon, SL, Scholz, SW, Priebe, T, Öttl, M, Dong, J, Meijer, M, Janssen, LJM, Lourenco, VS, van der Kant, R, Crusius, D, Paquet, D, Raulin, AC, Bu, G, Held, A, Wainger, BJ, Gabriele, RMC, Casey, JM, Wray, S, Abu-Bonsrah, D, Parish, CL, Beccari, MS, Cleveland, DW, Li, E, Rose, IVL, Kampmann, M, Calatayud Aristoy, C, Verstreken, P, Heinrich, L, Chen, MY, Schüle, B, Dou, D, Holzbaur, ELF, Zanellati, MC, Basundra, R, Deshmukh, M, Cohen, S, Khanna, R, Raman, M, Nevin, ZS, Matia, M, Van Lent, J, Timmerman, V, Conklin, BR, Johnson Chase, K, Zhang, K, Funes, S, Bosco, DA, Erlebach, L, Welzer, M, Kronenberg-Versteeg, D, Lyu, G, Arenas, E, Coccia, E, Sarrafha, L, Ahfeldt, T, Marioni, JC, Skarnes, WC, Cookson, MR, Ward, ME & Merkle, FT 2022, 'A reference human induced pluripotent stem cell line for large-scale collaborative studies', Cell Stem Cell, vol. 29, no. 12, pp. 1685-1702.e22. https://doi.org/10.1016/j.stem.2022.11.004

@article{f8a759dc746c4233b4250380fe009e96,

title = "A reference human induced pluripotent stem cell line for large-scale collaborative studies",

abstract = "Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.",

keywords = "CRISPR, differentiation, iPSC, karyotype, p53, pluripotent, reference, single-cell, stem cell, whole-genome",

author = "Pantazis, {Caroline B.} and Andrian Yang and Erika Lara and McDonough, {Justin A.} and Cornelis Blauwendraat and Lirong Peng and Hideyuki Oguro and Jitendra Kanaujiya and Jizhong Zou and David Sebesta and Gretchen Pratt and Erin Cross and Jeffrey Blockwick and Philip Buxton and Lauren Kinner-Bibeau and Constance Medura and Christopher Tompkins and Stephen Hughes and Marianita Santiana and Faraz Faghri and Nalls, {Mike A.} and Daniel Vitale and Shannon Ballard and Qi, {Yue A.} and Ramos, {Daniel M.} and Anderson, {Kailyn M.} and Julia Stadler and Priyanka Narayan and Jason Papademetriou and Luke Reilly and Nelson, {Matthew P.} and Sanya Aggarwal and Rosen, {Leah U.} and Peter Kirwan and Venkat Pisupati and Coon, {Steven L.} and Scholz, {Sonja W.} and Theresa Priebe and Miriam {\"O}ttl and Jian Dong and Marieke Meijer and Janssen, {Lara J.M.} and Lourenco, {Vanessa S.} and {van der Kant}, Rik and Dennis Crusius and Dominik Paquet and Raulin, {Ana Caroline} and Guojun Bu and Aaron Held and Wainger, {Brian J.} and Gabriele, {Rebecca M.C.} and Casey, {Jackie M.} and Selina Wray and Dad Abu-Bonsrah and Parish, {Clare L.} and Beccari, {Melinda S.} and Cleveland, {Don W.} and Emmy Li and Rose, {Indigo V.L.} and Martin Kampmann and {Calatayud Aristoy}, Carles and Patrik Verstreken and Laurin Heinrich and Chen, {Max Y.} and Birgitt Sch{\"u}le and Dan Dou and Holzbaur, {Erika L.F.} and Zanellati, {Maria Clara} and Richa Basundra and Mohanish Deshmukh and Sarah Cohen and Richa Khanna and Malavika Raman and Nevin, {Zachary S.} and Madeline Matia and {Van Lent}, Jonas and Vincent Timmerman and Conklin, {Bruce R.} and {Johnson Chase}, Katherine and Ke Zhang and Salome Funes and Bosco, {Daryl A.} and Lena Erlebach and Marc Welzer and Deborah Kronenberg-Versteeg and Guochang Lyu and Ernest Arenas and Elena Coccia and Lily Sarrafha and Tim Ahfeldt and Marioni, {John C.} and Skarnes, {William C.} and Cookson, {Mark R.} and Ward, {Michael E.} and Merkle, {Florian T.}",

note = "Funding Information: M.M. is supported by the ZonMw-Veni program (09150161810052) from the Dutch Research Council ( NWO ). R.v.d.K is supported by a CZI NDCN Pilot Grant (2020-222244(5022)). D.P. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany{\textquoteright}s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). M.S.B. is supported by a T32AG066596-01 training grant from the NIH. D.W.C. is funded by R01-NS27036. A.H. is supported by NRSA postdoctoral fellowship from the NIH (F32NS114319). B.J.W. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-I-R44). S.W. and R.G. are supported by Alzheimer{\textquoteright}s Research UK (ARUK-SRF2016B-2), the UCL Neurogenetic Therapies Program, generously funded by The Sigrid Rausing Trust and the National Institute for Health Research University College London Hospitals Biomedical Research Centre . E.L. is funded by the National Defense Science and Engineering Graduate Fellowship from the DoD . I.V.L.R. is funded by the California Institute for Regenerative Medicine Scholars Research Training Program (EDUC4-12812) and the Ruth L. Kirschstein National Research Service Award (T32 NS115706) from the NIH. M.K. is funded by a Chan Zuckerberg Initiative Ben Barres Early Career Acceleration award. P.V. is supported by Mission Lucidity, an ERC consolidator grant, and Research Foundation Flanders ( FWO ). C.C. is funded by the Marie Sk{\l}odowska-Curie Actions - Seal of Excellence FWO and postdoctoral fellowship. B.S. and P.V. are supported by the CZI NDCN and Amici Lovanienses . L.H. is funded by the DFG (471227244). D.D. was supported by T32-AG-000255 from the NIH. E.L.F.H. is funded by NINDS R01 NS060698. M.D. and S.C. are supported by a CZI NDCN Collaborative Pairs Award. M.R. is supported by a grant from the NIH (R01GM127557) and the Tufts Springboard Award ( Tufts University ). J.V.L. is supported by a DOC-PRO4 PhD fellowship from the University of Antwerp and an FWO-Flanders travel grant to perform the research at Gladstone Institute. K.J.C. and K.Z. are supported by grants from NIH- NINDS / NIA (R01NS117461), DoD (W81XWH-21-1-0082), Target ALS , and the Frick Foundation for ALS Research . Funding from the Dan and Diane Riccio Fund for Neuroscience, the Angel Fund for ALS research, and the Radala Foundation was provided to D.A.B. for this work. L.E. is supported by the Studienstiftung des deutschen Volkes and the International Max Planck Research School ( IMPRS ) for The Mechanisms of Mental Function and Dysfunction (MMFD). D.K-V. is supported by grants from the CZI (2020-221779(5022) & 2021-235147) and Alzheimer Forschung Initiative e.V. (20019p). G.L. and E.A. are supported by EU H2020-MSCA-ITN-2018 (813851), CZI NDCN (2018-191929), EU H2020-FETOPEN (HS-SEQ, 899687), Wallenberg Scholar (KAW2018.0232), ERC Advanced (PreciseCellPD, 884608), SSF (SB16-0065), VR (2020-01426), Hjarnfonden (FO2019-0068), Cancerfonden (CAN2016/572), and Karolinska Institutet (StratRegen 2018). L.S. is supported by the Training Program in Stem Cell Biology fellowship from the New York State Department of Health (NYSTEM-C32561GG). Funding Information: This research was supported in part by the Intramural Research Program of the NIH , National Institute on Aging (NIA), Department of Health and Human Services (ZO1 AG000535), as well as the National Institute of Neurological Disorders and Stroke (NINDS) . A.Y. is supported by an EMBL-EBI /Cambridge Computational Biomedical Postdoctoral Fellowship (EBPOD). V.P. is supported by a UK Regenerative Medicine Platform grant from the Medical Research Council (MR/R015724/1). F.T.M. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-R-156) and is supported by the Wellcome Trust and Royal Society (211221/Z/18/Z) and a Ben Barres Early Career Acceleration Award from the Chan Zuckerberg Initiative{\textquoteright}s Neurodegeneration Challenge Network ( CZI NDCN 191942) that supported the costs of directed differentiation and single-cell sequencing. J.C.M. acknowledges core funding from the European Molecular Biology Laboratory and from Cancer Research UK (C9545/A29580). We thank Greg Strachnan and the MRC Metabolic Diseases Unit Imaging Core Facility for assistance with imaging and Katarzyna Kania and the staff at the Genomics Core Facility of the Cancer Research UK Cambridge Institute for assistance with single-cell library preparation and sequencing. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA ( https://hpc.nih.gov/ ). This research has been conducted using the UK Biobank Resource under Application Number 33601. We gratefully acknowledge the contribution of the Scientific Services at the Jackson Laboratory for work described in this publication, including the Cellular Engineering service, the Genome Technologies service for expert assistance with whole genome sequencing and DNA and RNA preparation, the Flow Cytometry service for expertise in the p53 assay, the Cytogenetics laboratory for G-band karyotyping and analysis of several iPSC sub-lines, and Scientific Instrument Services. Funding Information: This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA), Department of Health and Human Services (ZO1 AG000535), as well as the National Institute of Neurological Disorders and Stroke (NINDS). A.Y. is supported by an EMBL-EBI/Cambridge Computational Biomedical Postdoctoral Fellowship (EBPOD). V.P. is supported by a UK Regenerative Medicine Platform grant from the Medical Research Council (MR/R015724/1). F.T.M. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-R-156) and is supported by the Wellcome Trust and Royal Society (211221/Z/18/Z) and a Ben Barres Early Career Acceleration Award from the Chan Zuckerberg Initiative's Neurodegeneration Challenge Network (CZI NDCN 191942) that supported the costs of directed differentiation and single-cell sequencing. J.C.M. acknowledges core funding from the European Molecular Biology Laboratory and from Cancer Research UK (C9545/A29580). We thank Greg Strachnan and the MRC Metabolic Diseases Unit Imaging Core Facility for assistance with imaging and Katarzyna Kania and the staff at the Genomics Core Facility of the Cancer Research UK Cambridge Institute for assistance with single-cell library preparation and sequencing. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA (https://hpc.nih.gov/). This research has been conducted using the UK Biobank Resource under Application Number 33601. We gratefully acknowledge the contribution of the Scientific Services at the Jackson Laboratory for work described in this publication, including the Cellular Engineering service, the Genome Technologies service for expert assistance with whole genome sequencing and DNA and RNA preparation, the Flow Cytometry service for expertise in the p53 assay, the Cytogenetics laboratory for G-band karyotyping and analysis of several iPSC sub-lines, and Scientific Instrument Services. M.M. is supported by the ZonMw-Veni program (09150161810052) from the Dutch Research Council (NWO). R.v.d.K is supported by a CZI NDCN Pilot Grant (2020-222244(5022)). D.P. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). M.S.B. is supported by a T32AG066596-01 training grant from the NIH. D.W.C. is funded by R01-NS27036. A.H. is supported by NRSA postdoctoral fellowship from the NIH (F32NS114319). B.J.W. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-I-R44). S.W. and R.G. are supported by Alzheimer's Research UK (ARUK-SRF2016B-2), the UCL Neurogenetic Therapies Program, generously funded by The Sigrid Rausing Trust and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. E.L. is funded by the National Defense Science and Engineering Graduate Fellowship from the DoD. I.V.L.R. is funded by the California Institute for Regenerative Medicine Scholars Research Training Program (EDUC4-12812) and the Ruth L. Kirschstein National Research Service Award (T32 NS115706) from the NIH. M.K. is funded by a Chan Zuckerberg Initiative Ben Barres Early Career Acceleration award. P.V. is supported by Mission Lucidity, an ERC consolidator grant, and Research Foundation Flanders (FWO). C.C. is funded by the Marie Sk{\l}odowska-Curie Actions - Seal of Excellence FWO and postdoctoral fellowship. B.S. and P.V. are supported by the CZI NDCN and Amici Lovanienses. L.H. is funded by the DFG (471227244). D.D. was supported by T32-AG-000255 from the NIH. E.L.F.H. is funded by NINDS R01 NS060698. M.D. and S.C. are supported by a CZI NDCN Collaborative Pairs Award. M.R. is supported by a grant from the NIH (R01GM127557) and the Tufts Springboard Award (Tufts University). J.V.L. is supported by a DOC-PRO4 PhD fellowship from the University of Antwerp and an FWO-Flanders travel grant to perform the research at Gladstone Institute. K.J.C. and K.Z. are supported by grants from NIH-NINDS/NIA (R01NS117461), DoD (W81XWH-21-1-0082), Target ALS, and the Frick Foundation for ALS Research. Funding from the Dan and Diane Riccio Fund for Neuroscience, the Angel Fund for ALS research, and the Radala Foundation was provided to D.A.B. for this work. L.E. is supported by the Studienstiftung des deutschen Volkes and the International Max Planck Research School (IMPRS) for The Mechanisms of Mental Function and Dysfunction (MMFD). D.K-V. is supported by grants from the CZI (2020-221779(5022) & 2021-235147) and Alzheimer Forschung Initiative e.V. (20019p). G.L. and E.A. are supported by EU H2020-MSCA-ITN-2018 (813851), CZI NDCN (2018-191929), EU H2020-FETOPEN (HS-SEQ, 899687), Wallenberg Scholar (KAW2018.0232), ERC Advanced (PreciseCellPD, 884608), SSF (SB16-0065), VR (2020-01426), Hjarnfonden (FO2019-0068), Cancerfonden (CAN2016/572), and Karolinska Institutet (StratRegen 2018). L.S. is supported by the Training Program in Stem Cell Biology fellowship from the New York State Department of Health (NYSTEM-C32561GG). All co-first authors (C.B.P. A.Y. E.L. J.A.M. C.B. and L.P.) contributed equally to this manuscript and all authors agree that they can both indicate their equal contribution and re-order the list of co-first authors in their own publication records. Conceptualization, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; methodology, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M; validation, A.Y. E.L. J.A.M. C.B. L.P. H.O. J.K. T.P. M.O. J.D. M.M. L.J.M.J. V.S.L. R.v.d.K. D.C. D.P. A.-C.R. G.B. A.H. B.J.W. R.M.C.G. J.M.C. S.W. D.A.-B. C.L.P. M.S.B. D.W.C. E.L. I.V.L.R. M.K. C.C.A. P.V. L.H. M.Y.C. B.S. D.D. E.L.F.H. M.C.Z. R.B. M.D. S.C. R.K. M.R. Z.S.N. M.M. J.V.L. B.R.C. K.J.C. K.E. S.F. D.A.B. L.E. M.W. D.K.-V. G.L. E.A. E.C. L.S. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; formal analysis, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. D.S. G.P. E.C. J.B. P.B. L.K.-B. C.M. C.T. S.H. W.C.S. M.R.C. M.E.W. F.T.M.; investigation, A.Y. E.L. J.A.M. C.B. L.P. H.O. J.K. J.Z. D.S. G.P. E.C. J.B. P.B. L.K.-B. C.M. C.T. S.H. M.S. F.F. M.A.N. D.V. S.B. Y.A.Q. D.M.R. K.A.M. J.P. L.R. M.P.N. S.A. L.U.R. P.K. V.P. S.L.C. S.W.S. T.P. M.{\"O}. J.D. M.M. L.J.M.J. V.S.L. R.v.d.K. D.C. D.P. A-C.R. G.B. A.H. B.J.W. R.M.C.G. J.M.C. S.W. D.A.-B. C.L.P. M.S.B. D.W.C. E.L. I.V.L.R. M.K. C.C.A. P.V. L.H. M.Y.C. B.S. D.D. E.L.F.H. M.C.Z. R.B. M.D. S.C. R.K. M.R. Z.S.N. M.M. J.V.L. B.R.C. K.J.C. K.E. S.F. D.A.B. L.E. M.W. D.K.-V. G.L. E.A. E.C. L.S. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; resources, all co-authors; data curation, C.B.P. A.Y. C.B. L.P. F.F. M.A.N. D.V. S.B.; writing – original draft, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. W.C.S. M.R.C. M.E.W. F.T.M; writing – reviewing & editing, all co-authors; supervision, J.Z. D.S. G.P. F.F. M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. V.T. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; visualization, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. H.O. J.K. J.Z. D.S. G.P. E.C. J.B. P.B. L.K.-B. C.M. C.T. S.H. M.S. K.M.A. T.P. M.O. J.D. M.M. L.J.M.J. V.S.L. R.v.d.K. D.C. D.P. A.-C.R. G.B. A.H. B.J.W. R.M.C.G. J.M.C. S.W. D.A.-B. C.L.P. M.S.B. D.W.C. E.L. I.V.L.R. M.K. C.C.A. P.V. L.H. M.Y.C. B.S. D.D. E.L.F.H. M.C.Z. R.B. M.D. S.C. R.K. M.R. Z.S.N. M.M. J.V.L. B.R.C. K.J.C. K.E. S.F. D.A.B. L.E. M.W. D.K.-V. G.L. E.A. E.C. L.S. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; project administration, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. H.O. J.Z. D.S. G.P. M.S. F.F. M.A.N. P.N. J.P. S.L.C. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; funding acquisition, M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. V.T. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. M.R.C. M.E.W. F.T.M. S.W.S. is on the scientific advisory council of the Lewy Body Dementia Association and the MSA Coalition. S.W.S. is an editorial board member for the Journal of Parkinson Disease and JAMA Neurology. S.W.S. received research support from Cerevel Therapeutics. M.K. serves on the scientific advisory boards of Engine Biosciences, Casma Therapeutics, Cajal Neuroscience, and Alector and is a consultant to Modulo Bio and Recursion Therapeutics. Participation by researchers from Data Tecnica International, LLC in this project was part of a competitive contract awarded to Data Tecnica International, LLC by the National Institutes of Health to support open science research. M.A.N. also currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc. E.A. is founder, shareholder, and scientific advisor of Cholestenix, Ltd. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = dec,

day = "1",

doi = "10.1016/j.stem.2022.11.004",

language = "English (US)",

volume = "29",

pages = "1685--1702.e22",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "12",

}

TY - JOUR

T1 - A reference human induced pluripotent stem cell line for large-scale collaborative studies

AU - Pantazis, Caroline B.

AU - Yang, Andrian

AU - Lara, Erika

AU - McDonough, Justin A.

AU - Blauwendraat, Cornelis

AU - Peng, Lirong

AU - Oguro, Hideyuki

AU - Kanaujiya, Jitendra

AU - Zou, Jizhong

AU - Sebesta, David

AU - Pratt, Gretchen

AU - Cross, Erin

AU - Blockwick, Jeffrey

AU - Buxton, Philip

AU - Kinner-Bibeau, Lauren

AU - Medura, Constance

AU - Tompkins, Christopher

AU - Hughes, Stephen

AU - Santiana, Marianita

AU - Faghri, Faraz

AU - Nalls, Mike A.

AU - Vitale, Daniel

AU - Ballard, Shannon

AU - Qi, Yue A.

AU - Ramos, Daniel M.

AU - Anderson, Kailyn M.

AU - Stadler, Julia

AU - Narayan, Priyanka

AU - Papademetriou, Jason

AU - Reilly, Luke

AU - Nelson, Matthew P.

AU - Aggarwal, Sanya

AU - Rosen, Leah U.

AU - Kirwan, Peter

AU - Pisupati, Venkat

AU - Coon, Steven L.

AU - Scholz, Sonja W.

AU - Priebe, Theresa

AU - Öttl, Miriam

AU - Dong, Jian

AU - Meijer, Marieke

AU - Janssen, Lara J.M.

AU - Lourenco, Vanessa S.

AU - van der Kant, Rik

AU - Crusius, Dennis

AU - Paquet, Dominik

AU - Raulin, Ana Caroline

AU - Bu, Guojun

AU - Held, Aaron

AU - Wainger, Brian J.

AU - Gabriele, Rebecca M.C.

AU - Casey, Jackie M.

AU - Wray, Selina

AU - Abu-Bonsrah, Dad

AU - Parish, Clare L.

AU - Beccari, Melinda S.

AU - Cleveland, Don W.

AU - Li, Emmy

AU - Rose, Indigo V.L.

AU - Kampmann, Martin

AU - Calatayud Aristoy, Carles

AU - Verstreken, Patrik

AU - Heinrich, Laurin

AU - Chen, Max Y.

AU - Schüle, Birgitt

AU - Dou, Dan

AU - Holzbaur, Erika L.F.

AU - Zanellati, Maria Clara

AU - Basundra, Richa

AU - Deshmukh, Mohanish

AU - Cohen, Sarah

AU - Khanna, Richa

AU - Raman, Malavika

AU - Nevin, Zachary S.

AU - Matia, Madeline

AU - Van Lent, Jonas

AU - Timmerman, Vincent

AU - Conklin, Bruce R.

AU - Johnson Chase, Katherine

AU - Zhang, Ke

AU - Funes, Salome

AU - Bosco, Daryl A.

AU - Erlebach, Lena

AU - Welzer, Marc

AU - Kronenberg-Versteeg, Deborah

AU - Lyu, Guochang

AU - Arenas, Ernest

AU - Coccia, Elena

AU - Sarrafha, Lily

AU - Ahfeldt, Tim

AU - Marioni, John C.

AU - Skarnes, William C.

AU - Cookson, Mark R.

AU - Ward, Michael E.

AU - Merkle, Florian T.

N1 - Funding Information: M.M. is supported by the ZonMw-Veni program (09150161810052) from the Dutch Research Council ( NWO ). R.v.d.K is supported by a CZI NDCN Pilot Grant (2020-222244(5022)). D.P. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). M.S.B. is supported by a T32AG066596-01 training grant from the NIH. D.W.C. is funded by R01-NS27036. A.H. is supported by NRSA postdoctoral fellowship from the NIH (F32NS114319). B.J.W. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-I-R44). S.W. and R.G. are supported by Alzheimer’s Research UK (ARUK-SRF2016B-2), the UCL Neurogenetic Therapies Program, generously funded by The Sigrid Rausing Trust and the National Institute for Health Research University College London Hospitals Biomedical Research Centre . E.L. is funded by the National Defense Science and Engineering Graduate Fellowship from the DoD . I.V.L.R. is funded by the California Institute for Regenerative Medicine Scholars Research Training Program (EDUC4-12812) and the Ruth L. Kirschstein National Research Service Award (T32 NS115706) from the NIH. M.K. is funded by a Chan Zuckerberg Initiative Ben Barres Early Career Acceleration award. P.V. is supported by Mission Lucidity, an ERC consolidator grant, and Research Foundation Flanders ( FWO ). C.C. is funded by the Marie Skłodowska-Curie Actions - Seal of Excellence FWO and postdoctoral fellowship. B.S. and P.V. are supported by the CZI NDCN and Amici Lovanienses . L.H. is funded by the DFG (471227244). D.D. was supported by T32-AG-000255 from the NIH. E.L.F.H. is funded by NINDS R01 NS060698. M.D. and S.C. are supported by a CZI NDCN Collaborative Pairs Award. M.R. is supported by a grant from the NIH (R01GM127557) and the Tufts Springboard Award ( Tufts University ). J.V.L. is supported by a DOC-PRO4 PhD fellowship from the University of Antwerp and an FWO-Flanders travel grant to perform the research at Gladstone Institute. K.J.C. and K.Z. are supported by grants from NIH- NINDS / NIA (R01NS117461), DoD (W81XWH-21-1-0082), Target ALS , and the Frick Foundation for ALS Research . Funding from the Dan and Diane Riccio Fund for Neuroscience, the Angel Fund for ALS research, and the Radala Foundation was provided to D.A.B. for this work. L.E. is supported by the Studienstiftung des deutschen Volkes and the International Max Planck Research School ( IMPRS ) for The Mechanisms of Mental Function and Dysfunction (MMFD). D.K-V. is supported by grants from the CZI (2020-221779(5022) & 2021-235147) and Alzheimer Forschung Initiative e.V. (20019p). G.L. and E.A. are supported by EU H2020-MSCA-ITN-2018 (813851), CZI NDCN (2018-191929), EU H2020-FETOPEN (HS-SEQ, 899687), Wallenberg Scholar (KAW2018.0232), ERC Advanced (PreciseCellPD, 884608), SSF (SB16-0065), VR (2020-01426), Hjarnfonden (FO2019-0068), Cancerfonden (CAN2016/572), and Karolinska Institutet (StratRegen 2018). L.S. is supported by the Training Program in Stem Cell Biology fellowship from the New York State Department of Health (NYSTEM-C32561GG). Funding Information: This research was supported in part by the Intramural Research Program of the NIH , National Institute on Aging (NIA), Department of Health and Human Services (ZO1 AG000535), as well as the National Institute of Neurological Disorders and Stroke (NINDS) . A.Y. is supported by an EMBL-EBI /Cambridge Computational Biomedical Postdoctoral Fellowship (EBPOD). V.P. is supported by a UK Regenerative Medicine Platform grant from the Medical Research Council (MR/R015724/1). F.T.M. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-R-156) and is supported by the Wellcome Trust and Royal Society (211221/Z/18/Z) and a Ben Barres Early Career Acceleration Award from the Chan Zuckerberg Initiative’s Neurodegeneration Challenge Network ( CZI NDCN 191942) that supported the costs of directed differentiation and single-cell sequencing. J.C.M. acknowledges core funding from the European Molecular Biology Laboratory and from Cancer Research UK (C9545/A29580). We thank Greg Strachnan and the MRC Metabolic Diseases Unit Imaging Core Facility for assistance with imaging and Katarzyna Kania and the staff at the Genomics Core Facility of the Cancer Research UK Cambridge Institute for assistance with single-cell library preparation and sequencing. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA ( https://hpc.nih.gov/ ). This research has been conducted using the UK Biobank Resource under Application Number 33601. We gratefully acknowledge the contribution of the Scientific Services at the Jackson Laboratory for work described in this publication, including the Cellular Engineering service, the Genome Technologies service for expert assistance with whole genome sequencing and DNA and RNA preparation, the Flow Cytometry service for expertise in the p53 assay, the Cytogenetics laboratory for G-band karyotyping and analysis of several iPSC sub-lines, and Scientific Instrument Services. Funding Information: This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA), Department of Health and Human Services (ZO1 AG000535), as well as the National Institute of Neurological Disorders and Stroke (NINDS). A.Y. is supported by an EMBL-EBI/Cambridge Computational Biomedical Postdoctoral Fellowship (EBPOD). V.P. is supported by a UK Regenerative Medicine Platform grant from the Medical Research Council (MR/R015724/1). F.T.M. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-R-156) and is supported by the Wellcome Trust and Royal Society (211221/Z/18/Z) and a Ben Barres Early Career Acceleration Award from the Chan Zuckerberg Initiative's Neurodegeneration Challenge Network (CZI NDCN 191942) that supported the costs of directed differentiation and single-cell sequencing. J.C.M. acknowledges core funding from the European Molecular Biology Laboratory and from Cancer Research UK (C9545/A29580). We thank Greg Strachnan and the MRC Metabolic Diseases Unit Imaging Core Facility for assistance with imaging and Katarzyna Kania and the staff at the Genomics Core Facility of the Cancer Research UK Cambridge Institute for assistance with single-cell library preparation and sequencing. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA (https://hpc.nih.gov/). This research has been conducted using the UK Biobank Resource under Application Number 33601. We gratefully acknowledge the contribution of the Scientific Services at the Jackson Laboratory for work described in this publication, including the Cellular Engineering service, the Genome Technologies service for expert assistance with whole genome sequencing and DNA and RNA preparation, the Flow Cytometry service for expertise in the p53 assay, the Cytogenetics laboratory for G-band karyotyping and analysis of several iPSC sub-lines, and Scientific Instrument Services. M.M. is supported by the ZonMw-Veni program (09150161810052) from the Dutch Research Council (NWO). R.v.d.K is supported by a CZI NDCN Pilot Grant (2020-222244(5022)). D.P. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). M.S.B. is supported by a T32AG066596-01 training grant from the NIH. D.W.C. is funded by R01-NS27036. A.H. is supported by NRSA postdoctoral fellowship from the NIH (F32NS114319). B.J.W. is a New York Stem Cell Foundation - Robertson Investigator (NYSCF-I-R44). S.W. and R.G. are supported by Alzheimer's Research UK (ARUK-SRF2016B-2), the UCL Neurogenetic Therapies Program, generously funded by The Sigrid Rausing Trust and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. E.L. is funded by the National Defense Science and Engineering Graduate Fellowship from the DoD. I.V.L.R. is funded by the California Institute for Regenerative Medicine Scholars Research Training Program (EDUC4-12812) and the Ruth L. Kirschstein National Research Service Award (T32 NS115706) from the NIH. M.K. is funded by a Chan Zuckerberg Initiative Ben Barres Early Career Acceleration award. P.V. is supported by Mission Lucidity, an ERC consolidator grant, and Research Foundation Flanders (FWO). C.C. is funded by the Marie Skłodowska-Curie Actions - Seal of Excellence FWO and postdoctoral fellowship. B.S. and P.V. are supported by the CZI NDCN and Amici Lovanienses. L.H. is funded by the DFG (471227244). D.D. was supported by T32-AG-000255 from the NIH. E.L.F.H. is funded by NINDS R01 NS060698. M.D. and S.C. are supported by a CZI NDCN Collaborative Pairs Award. M.R. is supported by a grant from the NIH (R01GM127557) and the Tufts Springboard Award (Tufts University). J.V.L. is supported by a DOC-PRO4 PhD fellowship from the University of Antwerp and an FWO-Flanders travel grant to perform the research at Gladstone Institute. K.J.C. and K.Z. are supported by grants from NIH-NINDS/NIA (R01NS117461), DoD (W81XWH-21-1-0082), Target ALS, and the Frick Foundation for ALS Research. Funding from the Dan and Diane Riccio Fund for Neuroscience, the Angel Fund for ALS research, and the Radala Foundation was provided to D.A.B. for this work. L.E. is supported by the Studienstiftung des deutschen Volkes and the International Max Planck Research School (IMPRS) for The Mechanisms of Mental Function and Dysfunction (MMFD). D.K-V. is supported by grants from the CZI (2020-221779(5022) & 2021-235147) and Alzheimer Forschung Initiative e.V. (20019p). G.L. and E.A. are supported by EU H2020-MSCA-ITN-2018 (813851), CZI NDCN (2018-191929), EU H2020-FETOPEN (HS-SEQ, 899687), Wallenberg Scholar (KAW2018.0232), ERC Advanced (PreciseCellPD, 884608), SSF (SB16-0065), VR (2020-01426), Hjarnfonden (FO2019-0068), Cancerfonden (CAN2016/572), and Karolinska Institutet (StratRegen 2018). L.S. is supported by the Training Program in Stem Cell Biology fellowship from the New York State Department of Health (NYSTEM-C32561GG). All co-first authors (C.B.P. A.Y. E.L. J.A.M. C.B. and L.P.) contributed equally to this manuscript and all authors agree that they can both indicate their equal contribution and re-order the list of co-first authors in their own publication records. Conceptualization, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; methodology, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M; validation, A.Y. E.L. J.A.M. C.B. L.P. H.O. J.K. T.P. M.O. J.D. M.M. L.J.M.J. V.S.L. R.v.d.K. D.C. D.P. A.-C.R. G.B. A.H. B.J.W. R.M.C.G. J.M.C. S.W. D.A.-B. C.L.P. M.S.B. D.W.C. E.L. I.V.L.R. M.K. C.C.A. P.V. L.H. M.Y.C. B.S. D.D. E.L.F.H. M.C.Z. R.B. M.D. S.C. R.K. M.R. Z.S.N. M.M. J.V.L. B.R.C. K.J.C. K.E. S.F. D.A.B. L.E. M.W. D.K.-V. G.L. E.A. E.C. L.S. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; formal analysis, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. D.S. G.P. E.C. J.B. P.B. L.K.-B. C.M. C.T. S.H. W.C.S. M.R.C. M.E.W. F.T.M.; investigation, A.Y. E.L. J.A.M. C.B. L.P. H.O. J.K. J.Z. D.S. G.P. E.C. J.B. P.B. L.K.-B. C.M. C.T. S.H. M.S. F.F. M.A.N. D.V. S.B. Y.A.Q. D.M.R. K.A.M. J.P. L.R. M.P.N. S.A. L.U.R. P.K. V.P. S.L.C. S.W.S. T.P. M.Ö. J.D. M.M. L.J.M.J. V.S.L. R.v.d.K. D.C. D.P. A-C.R. G.B. A.H. B.J.W. R.M.C.G. J.M.C. S.W. D.A.-B. C.L.P. M.S.B. D.W.C. E.L. I.V.L.R. M.K. C.C.A. P.V. L.H. M.Y.C. B.S. D.D. E.L.F.H. M.C.Z. R.B. M.D. S.C. R.K. M.R. Z.S.N. M.M. J.V.L. B.R.C. K.J.C. K.E. S.F. D.A.B. L.E. M.W. D.K.-V. G.L. E.A. E.C. L.S. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; resources, all co-authors; data curation, C.B.P. A.Y. C.B. L.P. F.F. M.A.N. D.V. S.B.; writing – original draft, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. W.C.S. M.R.C. M.E.W. F.T.M; writing – reviewing & editing, all co-authors; supervision, J.Z. D.S. G.P. F.F. M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. V.T. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; visualization, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. H.O. J.K. J.Z. D.S. G.P. E.C. J.B. P.B. L.K.-B. C.M. C.T. S.H. M.S. K.M.A. T.P. M.O. J.D. M.M. L.J.M.J. V.S.L. R.v.d.K. D.C. D.P. A.-C.R. G.B. A.H. B.J.W. R.M.C.G. J.M.C. S.W. D.A.-B. C.L.P. M.S.B. D.W.C. E.L. I.V.L.R. M.K. C.C.A. P.V. L.H. M.Y.C. B.S. D.D. E.L.F.H. M.C.Z. R.B. M.D. S.C. R.K. M.R. Z.S.N. M.M. J.V.L. B.R.C. K.J.C. K.E. S.F. D.A.B. L.E. M.W. D.K.-V. G.L. E.A. E.C. L.S. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; project administration, C.B.P. A.Y. E.L. J.A.M. C.B. L.P. H.O. J.Z. D.S. G.P. M.S. F.F. M.A.N. P.N. J.P. S.L.C. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. W.C.S. M.R.C. M.E.W. F.T.M.; funding acquisition, M.A.N. S.L.C. S.W.S. R.v.d.K. D.P. G.B. B.J.W. S.W. C.L.P. D.W.C. M.K. P.V. B.S. E.L.F.H. S.C. V.T. B.R.C. K.Z. D.A.B. D.K.-V. E.A. T.A. J.C.M. M.R.C. M.E.W. F.T.M. S.W.S. is on the scientific advisory council of the Lewy Body Dementia Association and the MSA Coalition. S.W.S. is an editorial board member for the Journal of Parkinson Disease and JAMA Neurology. S.W.S. received research support from Cerevel Therapeutics. M.K. serves on the scientific advisory boards of Engine Biosciences, Casma Therapeutics, Cajal Neuroscience, and Alector and is a consultant to Modulo Bio and Recursion Therapeutics. Participation by researchers from Data Tecnica International, LLC in this project was part of a competitive contract awarded to Data Tecnica International, LLC by the National Institutes of Health to support open science research. M.A.N. also currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc. E.A. is founder, shareholder, and scientific advisor of Cholestenix, Ltd. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: © 2022

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

AB - Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

KW - CRISPR

KW - differentiation

KW - iPSC

KW - karyotype

KW - p53

KW - pluripotent

KW - reference

KW - single-cell

KW - stem cell

KW - whole-genome

UR - http://www.scopus.com/inward/record.url?scp=85143156678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85143156678&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2022.11.004

DO - 10.1016/j.stem.2022.11.004

M3 - Article

C2 - 36459969

AN - SCOPUS:85143156678

SN - 1934-5909

VL - 29

SP - 1685-1702.e22

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 12

ER -

A reference human induced pluripotent stem cell line for large-scale collaborative studies

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