Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors

被引：669

作者：

Paul, Franziska ^{[1
]}

Arkin, Ya'ara ^{[2
,3
]}

Giladi, Amir ^{[1
]}

Jaitin, Diego Adhemar ^{[1
]}

Kenigsberg, Ephraim ^{[2
,3
]}

Keren-Shaul, Hadas ^{[1
]}

Winter, Deborah ^{[1
]}

Lara-Astiaso, David ^{[1
]}

Gury, Meital ^{[1
]}

Weiner, Assaf ^{[1
]}

David, Eyal ^{[1
]}

Cohen, Nadav ^{[2
,3
]}

Lauridsen, Felicia Kathrine Bratt ^{[4
,5
,6
]}

Haas, Simon ^{[7
]}

Schlitzer, Andreas ^{[8
,9
]}

Mildner, Alexander ^{[1
]}

Ginhoux, Florent ^{[8
]}

Jung, Steffen ^{[1
]}

Trumpp, Andreas

Porse, Bo Torben ^{[4
,5
,6
]}

Tanay, Amos ^{[2
,3
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel

[3] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

[4] Univ Copenhagen, Rigshosp, Finsen Lab, DK-2200 Copenhagen, Denmark

[5] BRIC, DK-2200 Copenhagen, Denmark

[6] Univ Copenhagen, Fac Hlth Sci, Danish Stem Cell Ctr DanStem, DK-2200 Copenhagen, Denmark

[7] Deutsch Krebsforschungszentrum, Div Stem Cells & Canc, D-69120 Heidelberg, Germany

[8] ASTAR, BIOPOLIS, Singapore Immunol Network SIgN, Singapore 138648, Singapore

[9] Univ Bonn, Life & Med Sci LIMES Inst, Genom & Immunoregulat, D-53115 Bonn, Germany

来源：

CELL | 2015年 / 163卷 / 07期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

HEMATOPOIETIC STEM-CELLS; C/EBP-ALPHA; SELF-RENEWAL; RNA-SEQ; EXPRESSION; GENE; DIFFERENTIATION; IDENTIFICATION; SPECIFICATION; MACROPHAGE;

D O I：

10.1016/j.cell.2015.11.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 sub-populations 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.

引用

页码：1663 / 1677

页数：15

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[1] Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment [J].