Kinetics of adult hematopoietic stem cell differentiation in vivo.
Kinetics of adult hematopoietic stem cell differentiation in vivo.
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DOI：
10.1084/jem.20180136
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发表时间：
2018-11-05
期刊：
影响因子：
--
通讯作者：
Reizis B
中科院分区：
文献类型：
--
作者：
Upadhaya S;Sawai CM;Papalexi E;Rashidfarrokhi A;Jang G;Chattopadhyay P;Satija R;Reizis B
造血干细胞（HSC）在稳态下产生不同血细胞类型的过程知之甚少。Upadhaya等人使用诱导谱系追踪来表征体内成体HSC分化的最早步骤。成人造血已被研究方面的祖细胞分化的潜力，而其在体内的动力学知之甚少。我们将内源性成体造血干细胞（HSC）的诱导谱系追踪与流式细胞术和单细胞RNA测序相结合，以表征稳态造血分化的早期步骤。标记的细胞，主要包括长期的HSC和一些短期的HSC，产生巨核细胞谱系后代在1周内的过程中，只需要两到三个细胞分裂。红系和髓系后代出现2周，同时包括一个祖细胞的人口与两个谱系的表达功能。在这个阶段的髓系祖细胞表现出多样化的粒细胞，单核细胞和树突状细胞类型，和罕见的中间细胞状态可以检测到。与此相反，淋巴样分化几乎是不存在的前3周的跟踪。这些结果表明，HSC的连续分化迅速产生主要的造血谱系和细胞类型，并揭示了巨核细胞、红细胞、髓细胞和淋巴样分化之间的基本动力学差异。
The process whereby hematopoietic stem cells (HSCs) generate different blood cell types in the steady-state is poorly understood. Upadhaya et al. used inducible lineage tracing to characterize the earliest steps of adult HSC differentiation in vivo. Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady-state. Labeled cells, comprising primarily long-term HSCs and some short-term HSCs, produced megakaryocytic lineage progeny within 1 wk in a process that required only two to three cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic, and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 wk of tracing. These results show that continuous differentiation of HSCs rapidly produces major hematopoietic lineages and cell types and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and lymphoid differentiation.
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