Clonal Analysis Unveils Self-Renewing Lineage-Restricted Progenitors Generated Directly from Hematopoietic Stem Cells

被引：526

作者：

Yamamoto, Ryo ^{[1
]}

Morita, Yohei ^{[1
,2
]}

Ooehara, Jun ^{[1
]}

Hamanaka, Sanae ^{[1
,3
]}

Onodera, Masafumi ^{[4
]}

Rudolph, Karl Lenhard ^{[2
]}

Ema, Hideo ^{[1
]}

Nakauchi, Hiromitsu ^{[1
,3
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Ctr Stem Cell Biol & Regenerat Med, Div Stem Cell Therapy,Minato Ku, Tokyo 1088639, Japan

[2] Fritz Lipmann Inst, Leibniz Inst Age Res, D-07745 Jena, Germany

[3] Japan Sci & Technol Agcy, ERATO, Nakauchi Stem Cell & Organ Regenerat Project, Minato Ku, Tokyo 1088639, Japan

[4] Natl Res Inst Child Hlth & Dev, Dept Human Genet, Setagaya Ku, Tokyo 1578535, Japan

来源：

CELL | 2013年 / 154卷 / 05期

关键词：

MOUSE BONE-MARROW; LONG-TERM; MULTIPOTENT PROGENITORS; DIFFERENTIATION; COMMITMENT; RECONSTITUTION; IDENTIFICATION; HETEROGENEITY; PROGRAMS; NOTCH;

D O I：

10.1016/j.cell.2013.08.007

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：

Consensus holds that hematopoietic stem cells (HSCs) give rise to multipotent progenitors (MPPs) of reduced self-renewal potential and that MPPs eventually produce lineage-committed progenitor cells in a stepwise manner. Using a single-cell transplantation system and marker mice, we unexpectedly found myeloid-restricted progenitors with long-term repopulating activity (MyRPs), which are lineage-committed to megakaryocytes, megakaryocyte-erythroid cells, or common myeloid cells (MkRPs, MERPs, or CMRPs, respectively) in the phenotypically defined HSC compartment together with HSCs. Paired daughter cell assays combined with transplantation revealed that HSCs can give rise to HSCs via symmetric division or directly differentiate into MyRPs via asymmetric division (yielding HSC-MkRP or HSC-CMRP pairs). These myeloid bypass pathways could be essential for fast responses to ablation stress. Our results show that loss of self-renewal and stepwise progression through specific differentiation stages are not essential for lineage commitment of HSCs and suggest a revised model of hematopoietic differentiation.

引用

页码：1112 / 1126

页数：15

共 35 条

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