Quantitative analysis of signaling responses during mouse primordial germ cell specification.
Quantitative analysis of signaling responses during mouse primordial germ cell specification.
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DOI：
10.1242/bio.058741
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发表时间：
2021-05-15
期刊：
影响因子：
2.4
通讯作者：
Hadjantonakis AK
中科院分区：
文献类型：
--
作者：
Morgani SM;Hadjantonakis AK
在哺乳动物早期发育过程中，胚胎的多能细胞暴露于驱动退出多能性和胚层分化的信号组合。与此同时，一小群多能细胞产生原始生殖细胞（PGC），即精子和卵子的前体，将可遗传的遗传信息传递给下一代。尽管 PGC 很重要，但仍不清楚它们首先是如何从体细胞中分离出来的，以及这是否涉及对其信号环境的不同反应。为了研究这个问题，我们以单细胞分辨率在体外和体内绘制了 PGC 及其周围微环境随时间变化的 BMP、MAPK 和 WNT 信号反应图谱。我们发现，在小鼠胚胎中，与邻近的胚胎外中胚层细胞相比，早期 PGC 表现出较低的 BMP 和 MAPK 反应，这表明种系与体细胞中出现了不同的信号调节机制。相比之下，PGC 和体细胞对 WNT 的反应相当，表明仅此信号不足以促进体细胞分化。最后，我们研究了 BMP 响应对这些细胞命运决定的要求。我们发现，BMP 受体 (Bmpr1a−/−) 发生突变的细胞系（其 BMP 信号传导反应受损）可以有效地生成 PGC 样细胞，这表明规范的 BMP 信号传导并不是细胞自主地指导 PGC 样分化所需的。摘要：胚胎的多能细胞亚群产生原始生殖细胞（PGC），即精子和卵子的前体，将可遗传的遗传信息传递给下一代。为了确定 PGC 是如何首先从体细胞中分离出来的，我们在体外和体内以单细胞分辨率研究了 PGC 及其周围微环境中 BMP、MAPK 和 WNT 信号随时间的变化。
During early mammalian development, the pluripotent cells of the embryo are exposed to a combination of signals that drive exit from pluripotency and germ layer differentiation. At the same time, a small population of pluripotent cells give rise to the primordial germ cells (PGCs), the precursors of the sperm and egg, which pass on heritable genetic information to the next generation. Despite the importance of PGCs, it remains unclear how they are first segregated from the soma, and if this involves distinct responses to their signaling environment. To investigate this question, we mapped BMP, MAPK and WNT signaling responses over time in PGCs and their surrounding niche in vitro and in vivo at single-cell resolution. We showed that, in the mouse embryo, early PGCs exhibit lower BMP and MAPK responses compared to neighboring extraembryonic mesoderm cells, suggesting the emergence of distinct signaling regulatory mechanisms in the germline versus soma. In contrast, PGCs and somatic cells responded comparably to WNT, indicating that this signal alone is not sufficient to promote somatic differentiation. Finally, we investigated the requirement of a BMP response for these cell fate decisions. We found that cell lines with a mutation in the BMP receptor (Bmpr1a−/−), which exhibit an impaired BMP signaling response, can efficiently generate PGC-like cells revealing that canonical BMP signaling is not cell autonomously required to direct PGC-like differentiation. Summary: A subpopulation of pluripotent cells of the embryo give rise to the primordial germ cells (PGCs), the precursors of the sperm and egg, which pass on heritable genetic information to the next generation. To determine how PGCs are first segregated from the soma, we investigated BMP, MAPK and WNT signaling over time in PGCs and their surrounding niche in vitro and in vivo at single-cell resolution.
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