Clonal analysis of lineage fate in native haematopoiesis.
Clonal analysis of lineage fate in native haematopoiesis.
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DOI：
10.1038/nature25168
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发表时间：
2018-01-11
期刊：
影响因子：
64.8
通讯作者：
Camargo FD
中科院分区：
文献类型：
--
作者：
Rodriguez-Fraticelli AE;Wolock SL;Weinreb CS;Panero R;Patel SH;Jankovic M;Sun J;Calogero RA;Klein AM;Camargo FD
造血，即成熟的血液和免疫细胞的产生过程，在功能上是一个层次结构，自我更新的造血干细胞(HSCs)和多能祖细胞(MPP)位于最顶端。关于这些原始造血室中最早的谱系选择是什么，细胞中间体，以及由此产生的谱系树，已经提出了多种模型。鉴于大部分关于谱系结局的研究都是在造血移植的背景下进行的，目前的谱系分支模型更有可能代表谱系潜力的路线图，而不是原生命运。在这里，我们利用转座子(TN)标记来克隆地追踪未受干扰的造血中的祖细胞和干细胞的命运。我们的结果描述了一个独特的克隆路线图，在这个路线图中，巨核细胞(Mk)谱系在很大程度上独立于其他造血命运。我们的数据结合单细胞RNAseq，确定了MPP群体中产生单链和寡链克隆的功能层次。最后，我们的结果表明，传统定义的长期造血干细胞(LT-HSCs)是Mk限制性祖细胞的重要来源，这表明Mk谱系是LT-HSCs的主要天然命运。我们的研究为无干扰的造血路线图的实质性修订提供了证据，并强调了MPPS和HSCs在原位的独特性质。
Hematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing hematopoietic stem cells (HSCs) and multipotent progenitor (MPP) cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive hematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of hematopoietic transplantation, current lineage branching models are more likely to represent roadmaps of lineage potential rather than native fate. Here, we utilize transposon (Tn) tagging to clonally trace the fates of progenitors and stem cells in unperturbed hematopoiesis. Our results describe a distinct clonal roadmap in which the megakaryocyte (Mk) lineage arises largely independently of other hematopoietic fates. Our data, combined with single cell RNAseq, identify a functional hierarchy of uni- and oligolineage producing clones within the MPP population. Finally, our results demonstrate that traditionally defined long-term HSCs (LT-HSCs) are a significant source of Mk-restricted progenitors, suggesting that the Mk-lineage is the predominant native fate of LT-HSCs. Our study provides evidence for a substantially revised roadmap for unperturbed hematopoiesis, and highlights unique properties of MPPs and HSCs in situ.
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DOI：
10.1002/stem.1985
发表时间：
2015-07
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Nishikii H;Kanazawa Y;Umemoto T;Goltsev Y;Matsuzaki Y;Matsushita K;Yamato M;Nolan GP;Negrin R;Chiba S
通讯作者：
Chiba S
影响因子：
64.8
作者：
Busch, Katrin;Klapproth, Kay;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
影响因子：
100.3
作者：
Ceredig, Rhodri;Rolink, Antonius G.;Brown, Geoffrey
通讯作者：
Brown, Geoffrey
影响因子：
32.4
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
通讯作者：
Reizis B