Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions

被引：530

作者：

Pietras, Eric M. ^{[1
]}

Reynaud, Damien ^{[1
]}

Kang, Yoon-A. ^{[1
]}

Carlin, Daniel ^{[2
,3
]}

Calero-Nieto, Fernando J. ^{[4
,5
,6
]}

Leavitt, Andrew D. ^{[7
,8
]}

Stuart, Joshua M. ^{[2
,3
]}

Goettgens, Berthold ^{[4
,5
,6
]}

Passegue, Emmanuelle ^{[1
]}

机构：

[1] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Div Hematol Oncol, Dept Med, San Francisco, CA 94143 USA

[2] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 94720 USA

[3] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 94720 USA

[4] Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Cambridge CB2 0XY, England

[5] Wellcome Trust Res Labs, Cambridge CB2 0XY, England

[6] MRC Cambridge Stem Cell Inst, Cambridge CB2 0XY, England

[7] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[8] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

来源：

CELL STEM CELL | 2015年 / 17卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

HEMATOPOIETIC STEM-CELLS; SELF-RENEWAL; HETEROGENEITY; DIFFERENTIATION; IDENTIFICATION; RECONSTITUTION; SPECIFICATION; EXPRESSION; HIERARCHY; REVEAL;

D O I：

10.1016/j.stem.2015.05.003

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Despite great advances in understanding the mechanisms underlying blood production, lineage specification at the level of multipotent progenitors (MPPs) remains poorly understood. Here, we show that MPP2 and MPP3 are distinct myeloid-biased MPP subsets that work together with lymphoid-primed MPP4 cells to control blood production. We find that all MPPs are produced in parallel by hematopoietic stem cells (HSCs), but with different kinetics and at variable levels depending on hematopoietic demands. We also show that the normally rare myeloid-biased MPPs are transiently overproduced by HSCs in regenerating conditions, hence supporting myeloid amplification to rebuild the hematopoietic system. This shift is accompanied by a reduction in self-renewal activity in regenerating HSCs and reprogramming of MPP4 fate toward the myeloid lineage. Our results support a dynamic model of blood development in which HSCs convey lineage specification through independent production of distinct lineage-biased MPP subsets that, in turn, support lineage expansion and differentiation.

引用

页码：35 / 46

页数：12

共 41 条

[1]

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