Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.
Hematopoietic Stem Cells Are the Major Source of Multilineage Hematopoiesis in Adult Animals.
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DOI：
10.1016/j.immuni.2016.08.007
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发表时间：
2016-09-20
期刊：
影响因子：
32.4
通讯作者：
Reizis B
中科院分区：
文献类型：
--
作者：
Sawai CM;Babovic S;Upadhaya S;Knapp DJHF;Lavin Y;Lau CM;Goloborodko A;Feng J;Fujisaki J;Ding L;Mirny LA;Merad M;Eaves CJ;Reizis B
造血干细胞（hematopoieticstemcells，HSCs）是维持移植受者长期造血重建的重要细胞，但其在内源性稳态造血中的作用尚不清楚。特别是，最近的研究表明，HSC对成人免疫细胞发育的贡献相对较小。我们在连续移植过程中保持重建活性的一部分HSC中定向表达转基因。诱导遗传标记显示，转基因表达的HSC产生其他表型的HSC，证实了它们在分化层次中的最高位置。标记的HSC迅速地贡献于所有谱系的定向祖细胞以及成熟的髓样细胞和淋巴细胞，但不贡献于B-1a细胞或组织巨噬细胞。重要的是，标记的HSC在成年小鼠中产生了超过三分之二的所有骨髓细胞和血小板，并且这种贡献可以通过诱导的干扰素反应来加速。因此，经典定义的HSC在稳态和全身性细胞因子应答期间维持免疫细胞发育。造血干细胞在稳态造血中的作用仍存在争议。在这里，Sawai等人使用谱系追踪来揭示HSC在整个成年生活中对所有血细胞谱系的主要贡献，包括骨髓细胞和淋巴细胞。
Hematopoietic stem cells (HSCs) sustain long-term reconstitution of hematopoiesis in transplantation recipients, yet their role in the endogenous steady-state hematopoiesis remains unclear. In particular, recent studies suggested that HSCs provide a relatively minor contribution to immune cell development in the adults. We directed transgene expression in a fraction of HSCs that maintained reconstituting activity during serial transplantations. Inducible genetic labeling showed that transgene-expressing HSCs gave rise to other phenotypic HSCs, confirming their top position in the differentiation hierarchy. The labeled HSCs rapidly contributed to committed progenitors of all lineages and to mature myeloid cells and lymphocytes, but not to B-1a cells or tissue macrophages. Importantly, labeled HSCs gave rise to more than two-thirds of all myeloid cells and platelets in adult mice, and this contribution could be accelerated by an induced interferon response. Thus, classically defined HSCs maintain immune cell development in the steady state and during systemic cytokine responses. The role of hematopoietic stem cells (HSCs) in steady-state hematopoiesis remains controversial. Here, Sawai et al. use lineage tracing to reveal a major contribution of HSCs to all blood cell lineages, including myeloid cells and lymphocytes, throughout the adult life.