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Cell. 2015 Dec 17;163(7):1663-77. doi: 10.1016/j.cell.2015.11.013. Epub 2015 Nov 25.

Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors.

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
3
The Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen 2200, Denmark; Biotech Research and Innovation Centre (BRIC), Copenhagen 2200, Denmark; Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
4
Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
5
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), BIOPOLIS 138648, Singapore; Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
6
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), BIOPOLIS 138648, Singapore.
7
Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: amos.tanay@weizmann.ac.il.
8
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: ido.amit@weizmann.ac.il.

Erratum in

  • Cell. 2016 Jan 14;164(1-2):325.

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.

PMID:
26627738
DOI:
10.1016/j.cell.2015.11.013
[Indexed for MEDLINE]
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