@article{0e54409a30804b4b827159575312f7ea,
title = "Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors",
abstract = "Human pluripotent stem cells (hPSCs) represent a promising source of patient-specific cells for disease modeling, drug screens, and cellular therapies. However, the inability to derive engraftable human hematopoietic stem and progenitor cells (HSPCs) has limited their characterization to in vitro assays. We report a strategy to respecify lineage-restricted CD34 +CD45+ myeloid precursors derived from hPSCs into multilineage progenitors that can be expanded in vitro and engrafted in vivo. HOXA9, ERG, and RORA conferred self-renewal and multilineage potential in vitro and maintained primitive CD34+CD38- cells. Screening cells via transplantation revealed that two additional factors, SOX4 and MYB, conferred engraftment. Progenitors specified with all five factors gave rise to reproducible short-term engraftment with myeloid and erythroid lineages. Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic and activating adult globin expression. Our combinatorial screening approach establishes a strategy for obtaining transcription-factor-mediated engraftment of blood progenitors from human pluripotent cells.",
author = "Sergei Doulatov and Vo, {Linda T.} and Chou, {Stephanie S.} and Kim, {Peter G.} and Natasha Arora and Hu Li and Hadland, {Brandon K.} and Bernstein, {Irwin D.} and Collins, {James J.} and Zon, {Leonard I.} and Daley, {George Q.}",
note = "Funding Information: The authors would like to thank Thorsten Schlaeger and the BCH ESC core, Ronald Mathieu from the flow cytometry core, and Norman Gerry from the Coriell Genotyping and Microarray Center for assistance. Andrea Ditadi and Gordon Keller provided reagents and advice. Band3 antibody was a gift from the Narla Mohandas lab. This work is supported by grants from the US National Institute of Diabetes and Digestive and Kidney Diseases (R24-DK092760) and the National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium (UO1-HL100001); Alex{\textquoteright}s Lemonade Stand; and the Doris Duke Medical Foundation. G.Q.D. is an associate member of the Broad Institute and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. S.D. is supported by a fellowship from the Helen Hay Whitney Foundation. L.T.V. is supported by the NSF Graduate Research Fellowship. ",
year = "2013",
month = oct,
day = "3",
doi = "10.1016/j.stem.2013.09.002",
language = "English (US)",
volume = "13",
pages = "459--470",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "4",
}