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Transcriptional heterogeneity and lineage commitment in myeloid progenitors

Item Type:Article
Title:Transcriptional heterogeneity and lineage commitment in myeloid progenitors
Creators Name:Paul, F. and Arkin, Y. and Giladi, A. and Jaitin, D.A. and Kenigsberg, E. and Keren-Shaul, H. and Winter, D. and Lara-Astiaso, D. and Gury, M. and Weiner, A. and David, E. and Cohen, N. and Lauridsen, F.K.B. and Haas, S. and Schlitzer, A. and Mildner, A. and Ginhoux, F. and Jung, S. and Trumpp, A. and Porse, B.T. and Tanay, A. and Amit, I.
Abstract:Within the bone marrow, stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with in vivo differentiation potential or gene regulatory mechanisms. Here, we comprehensively map myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups, showing unexpected transcriptional priming toward seven differentiation fates but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting that the process is tightly regulated. Histone maps and knockout assays are consistent with early transcriptional priming, while traditional transplantation experiments suggest that in vivo priming may still allow for plasticity given strong perturbations. These data establish a reference model and general framework for studying hematopoiesis at single-cell resolution.
Keywords:Bone Marrow Transplantation, CCAAT-Enhancer-Binding Proteins, Gene Knockout Techniques, Hematopoiesis, High-Throughput Nucleotide Sequencing, Inbred C57BL Mice, Myeloid Progenitor Cells, RNA Sequence Analysis, Single-Cell Analysis, Transcription Factors, Transcriptome, Animals, Mice
Publisher:Cell Press
Page Range:1663-1677
Date:17 December 2015
Additional Information:Erratum in: Cell 164(1-2): 325
Official Publication:https://doi.org/10.1016/j.cell.2015.11.013
PubMed:View item in PubMed

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