@article{72a9016c7be4489092b3ca691f140381,
title = "Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome",
abstract = "Gu and colleagues provide direct evidence that a developmentally impaired endocardium underlies the ventricular and valvular hypoplasia in hypoplastic left heart syndrome (HLHS) and relate recently discovered de novo mutations to the pathogenesis of this condition.",
keywords = "ETS1, NOTCH, de novo mutation, endocardium, endothelial to mesenchymal transition, fibronectin, human heart tissue, hypoplastic left heart syndrome, induced pluripotent stem cells, single-cell RNA-seq",
author = "Yifei Miao and Lei Tian and Marcy Martin and Paige, {Sharon L.} and Galdos, {Francisco X.} and Jibiao Li and Alyssa Klein and Hao Zhang and Ning Ma and Yuning Wei and Maria Stewart and Soah Lee and Moonen, {Jan Renier} and Bing Zhang and Paul Grossfeld and Seema Mital and David Chitayat and Wu, {Joseph C.} and Marlene Rabinovitch and Nelson, {Timothy J.} and Shuyi Nie and Wu, {Sean M.} and Mingxia Gu",
note = "Funding Information: We thank Drs. Jingjing Li, Qing Liu, Michael P. Snyder, and Mr. Eric Wei for DNM analysis and scRNA-seq sample preparation. We thank Ms. Julia Ryan for technical assistance with generation of iPSC-CMs. We greatly appreciate the administrative help of Ms. Michelle Fox. We also thank Drs. Mark Mercola, Kristy Red-Horse, Kyle Loh, Virginia D. Winn, and James Wells for providing intellectual consultation to the project. We also thank ReGen Theranostics, Inc., Rochester, MN as the manufacturer for the iPSC lines and Dr. William Pu from Boston Children{\textquoteright}s Hospital, Harvard Medical School who provided GFP and ETS1 overexpression lentivirus. This work was supported by the Hoffman/Schroepfer single ventricle gift fund from Stanford University , United States; the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome from Mayo Clinic, United States (T.J.N.); NIH 2R24HD000836-52 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (The University of Washington Birth Defects Research Laboratory); and AHA 20POST35210924 from Amerian Heart Association, United States (L.T.). Funding Information: We thank Drs. Jingjing Li, Qing Liu, Michael P. Snyder, and Mr. Eric Wei for DNM analysis and scRNA-seq sample preparation. We thank Ms. Julia Ryan for technical assistance with generation of iPSC-CMs. We greatly appreciate the administrative help of Ms. Michelle Fox. We also thank Drs. Mark Mercola, Kristy Red-Horse, Kyle Loh, Virginia D. Winn, and James Wells for providing intellectual consultation to the project. We also thank ReGen Theranostics, Inc. Rochester, MN as the manufacturer for the iPSC lines and Dr. William Pu from Boston Children's Hospital, Harvard Medical School who provided GFP and ETS1 overexpression lentivirus. This work was supported by the Hoffman/Schroepfer single ventricle gift fund from Stanford University, United States; the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome from Mayo Clinic, United States (T.J.N.); NIH 2R24HD000836-52 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (The University of Washington Birth Defects Research Laboratory); and AHA 20POST35210924 from Amerian Heart Association, United States (L.T.). Y.M. designed and performed experiments, analyzed data, and wrote the manuscript. L.T. designed and analyzed the scRNA-seq and bulk RNA-seq data and contributed to the writing of the manuscript. M.M. analyzed the imaging data and revised the manuscript. M.S. J.-R.M. and S.L. analyzed the imaging data. S.L.P. and F.X.G. provided iPSC-CMs and helped with experimental designs. J.L. and S.N. performed Ets1 knockout in Xenopus heart and analyzed the results. A.K. helped with knockdown and qPCR assays. Y.W. performed Ligand-receptor interaction analysis and consulted on scRNA-seq analysis. H.Z. and N.M. contributed to iPSC line maintenance, cell sorting, and contractility assay and provided human cardiac fibroblasts. B.Z. offered a substantial intellectual contribution to ETS1 ChIP-seq analysis. S.M. and D.C. provided human heart tissue sections and revised the manuscript. T.J.N. provided HLHS iPSC lines. S.M. J.C.W. M.R. and S.M.W. offered a substantial intellectual contribution to the project and revised the manuscript. M.G. designed the studies and oversaw the scRNA-seq, EC functional assays, data acquisition and analysis, and manuscript preparation and editing. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
day = "1",
doi = "10.1016/j.stem.2020.07.015",
language = "English (US)",
volume = "27",
pages = "574--589.e8",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}