Screening for genes that regulate the differentiation of human megakaryocytic lineage cells

Proceedings of the National Academy of Sciences of the United States of America
Fangfang ZhuIrving L Weissman

Abstract

Different combinations of transcription factors (TFs) function at each stage of hematopoiesis, leading to distinct expression patterns of lineage-specific genes. The identification of such regulators and their functions in hematopoiesis remain largely unresolved. In this study, we utilized screening approaches to study the transcriptional regulators of megakaryocyte progenitor (MkP) generation, a key step before platelet production. Promising candidate genes were generated from a microarray platform gene expression commons and individually manipulated in human hematopoietic stem and progenitor cells (HSPCs). Deletion of some of the candidate genes (the hit genes) by CRISPR/Cas9 led to decreased MkP generation during HSPC differentiation, while more MkPs were produced when some hit genes were overexpressed in HSPCs. We then demonstrated that overexpression of these genes can increase the frequency of mature megakaryocytic colonies by functional colony forming unit-megakaryocyte (CFU-Mk) assay and the release of platelets after in vitro maturation. Finally, we showed that the histone deacetylase inhibitors could also increase MkP differentiation, possibly by regulating some of the newly identified TFs. Therefore, identification o...Continue Reading

References

Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·H KeJ Friedman
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J FriedmanI Weissman
Apr 16, 1998·The Journal of Clinical Investigation·N UchidaI L Weissman
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·N UchidaI L Weissman
Dec 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Thanyaphong Na NakornIrving L Weissman
Oct 7, 2004·The Journal of Biological Chemistry·Pascale JackersDennis K Watson
Feb 20, 2007·Current Opinion in Immunology·Min Ye, Thomas Graf
Oct 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·John E PimandaBerthold Göttgens
Feb 26, 2008·Cell·Stuart H Orkin, Leonard I Zon
Aug 17, 2010·The International Journal of Developmental Biology·John E Pimanda, Berthold Göttgens
Oct 5, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Jun Seita, Irving L Weissman
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Mar 1, 2013·Blood·Alexander ZaslavskySandra Ryeom
Aug 13, 2013·Nature·Alejandra Sanjuan-PlaSten Eirik W Jacobsen
Dec 4, 2013·Genes & Development·Abba MalinaJerry Pelletier
Dec 18, 2013·Science·Tim WangEric S Lander
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Apr 26, 2014·The Journal of Clinical Investigation·Pratima ChaurasiaRonald Hoffman
May 30, 2014·Nature·Pietro GenoveseLuigi Naldini
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Jan 17, 2015·Cell·Charles K F ChanMichael T Longaker
Aug 28, 2015·Journal of Pharmacology & Pharmacotherapeutics·Cherukuri TejaswiKaliaperumal Karthikeyan
Oct 13, 2016·Cell Reports·Julian PulecioAngel Raya

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Citations

May 3, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Leila J NoetzliKellie R Machlus
Aug 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Fangfang ZhuIrving L Weissman
Sep 12, 2018·Proceedings of the National Academy of Sciences of the United States of America·Kenneth Kaushansky
Dec 23, 2020·Blood Advances·Anthony K YeungGeorge J Murphy
May 5, 2021·Blood Advances·Emilie MontenontJesse W Rowley
Aug 31, 2021·Frontiers in Cell and Developmental Biology·Huicong LiuFangfang Zhu

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