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The transcriptional landscape of hematopoietic stem cell ontogeny

Item Type:Article
Title:The transcriptional landscape of hematopoietic stem cell ontogeny
Creators Name:McKinney-Freeman, S. and Cahan, P. and Li, H. and Lacadie, S.A. and Huang, H.T. and Curran, M. and Loewer, S. and Naveiras, O. and Kathrein, K.L. and Konantz, M. and Langdon, E.M. and Lengerke, C. and Zon, L.I. and Collins, J.J. and Daley, G.Q.
Abstract:Transcriptome analysis of adult hematopoietic stem cells (HSCs) and their progeny has revealed mechanisms of blood differentiation and leukemogenesis, but a similar analysis of HSC development is lacking. Here, we acquired the transcriptomes of developing HSCs purified from >2,500 murine embryos and adult mice. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs undergoing specification, and definitive HSCs. We applied a network-biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development and functionally validated candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knockdown in zebrafish embryos. Moreover, we found that HSCs from in vitro differentiated embryonic stem cells closely resemble definitive HSCs, yet lack a Notch-signaling signature, likely accounting for their defective lymphopoiesis. Our analysis and web resource will enhance efforts to identify regulators of HSC ontogeny and facilitate the engineering of hematopoietic specification.
Keywords:Cell Differentiation, Embryonic Stem Cells, Gene Expression Profiling, Hematopoietic Stem Cells, Yolk Sac, Animals, Mice, Zebrafish
Source:Cell Stem Cell
Publisher:Cell Press
Page Range:701-714
Date:2 November 2012
Official Publication:https://doi.org/10.1016/j.stem.2012.07.018
PubMed:View item in PubMed

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