Single-cell characterization of haematopoietic progenitors and their trajectories in homeostasis and perturbed haematopoiesis

被引：247

作者：

Giladi, Amir ^{[1
]}

Paul, Franziska ^{[1
]}

Herzog, Yoni ^{[2
]}

Lubling, Yaniv ^{[2
]}

Weiner, Assaf ^{[1
]}

Yofe, Ido ^{[1
]}

Jaitin, Diego ^{[1
]}

Cabezas-Wallscheid, Nina ^{[3
,4
,5
,6
]}

Dress, Regine ^{[7
]}

Ginhoux, Florent ^{[7
]}

Trumpp, Andreas ^{[3
,4
]}

Tanay, Amos ^{[2
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[2] Weizmann Inst Sci, Dept Regulat Biol, Dept Comp Sci & Appl Math, Rehovot, Israel

[3] Deutsch Krebsforschungszentrum DKFZ, Div Stem Cells & Canc, Heidelberg, Germany

[4] DKFZ ZMBH Alliance, Heidelberg, Germany

[5] Heidelberg Inst Stem Cell Technol & Expt Med HI S, Heidelberg, Germany

[6] Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany

[7] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore

来源：

NATURE CELL BIOLOGY | 2018年 / 20卷 / 07期

基金：

欧洲研究理事会; 以色列科学基金会;

关键词：

MOUSE BONE-MARROW; STEM-CELLS; LINEAGE-COMMITMENT; RNA-SEQ; IN-VIVO; IDENTIFICATION; DIFFERENTIATION; DYNAMICS; PU.1; HIERARCHY;

D O I：

10.1038/s41556-018-0121-4

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The dynamics of haematopoietic stem cell differentiation and the hierarchy of oligopotent stem cells in the bone marrow remain controversial. Here we dissect haematopoietic progenitor populations at single cell resolution, deriving an unbiased reference model of transcriptional states in normal and perturbed murine bone marrow. We define the signature of the naive haematopoietic stem cell and find a continuum of core progenitor states. Core cell populations mix transcription of pre-myeloid and prelymphoid programs, but do not mix erythroid or megakaryocyte programs with other fates. CRISP-seq perturbation analysis confirms our models and reveals that Cebpa regulates entry into all myeloid fates, while Irf8 and PU.1 deficiency block later differentiation towards monocyte or granulocyte fates. Our transcriptional map defines a reference network model for blood progenitors and their differentiation trajectories during normal and perturbed haematopoiesis.

引用

页码：836 / +

页数：13

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