Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs
Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs
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DOI：
10.1038/s41467-018-07769-8
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发表时间：
2018-12-20
影响因子：
16.6
通讯作者：
McKinney-Freeman, Shannon
中科院分区：
文献类型：
--
作者：
Ganuza, Miguel;Chabot, Ashley;McKinney-Freeman, Shannon
造血干细胞（dHSC）起源的胚胎部位已经争论了几十年。虽然胚胎内起源得到了很好的支持，卵黄囊（YS）成人造血的贡献仍然存在争议。相同的发育起源使得难以使用谱系追踪方法鉴定区分胚胎内起源与YS起源的特定标记。此外，血细胞的高度迁移性和循环前胚胎细胞的无能（即，5-7体节对（SP））在移植中甚至在培养后也能稳健地嫁接，这使得科学家无法正确地回答这些问题。在这里，我们报告了来自培养的2-7sp鼠胚胎外植体（Em-Ex）的稳健的、多谱系的和可连续移植的dHSC活性。在2-7sp YS外植体中检测不到dHSC。此外，Em-Ex的植入仅限于新兴的CD 31（+）CD 45（+）c-Kit（+）CD 41（-）群体。总之，我们的工作支持了一个模型，其中胚胎，而不是YS，是终身决定性造血的主要来源。
The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. The same developmental origin makes it difficult to identify specific markers that discern between an intraembryonic versus YS-origin using a lineage trace approach. Additionally, the highly migratory nature of blood cells and the inability of pre-circulatory embryonic cells (i.e., 5-7 somite pairs (sp)) to robustly engraft in transplantation, even after culture, has precluded scientists from properly answering these questions. Here we report robust, multi-lineage and serially transplantable dHSC activity from cultured 2-7sp murine embryonic explants (Em-Ex). dHSC are undetectable in 2-7sp YS explants. Additionally, the engraftment from Em-Ex is confined to an emerging CD31(+)CD45(+)c-Kit(+)CD41(-) population. In sum, our work supports a model in which the embryo, not the YS, is the major source of lifelong definitive hematopoiesis.