FGF, Insulin, and SMAD Signaling Cooperate for Avian Primordial Germ Cell Self-Renewal.
FGF, Insulin, and SMAD Signaling Cooperate for Avian Primordial Germ Cell Self-Renewal.
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DOI：
10.1016/j.stemcr.2015.10.008
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发表时间：
2015-12-08
影响因子：
5.9
通讯作者：
McGrew MJ
中科院分区：
文献类型：
--
作者：
Whyte J;Glover JD;Woodcock M;Brzeszczynska J;Taylor L;Sherman A;Kaiser P;McGrew MJ
生殖细胞谱系的精确自我更新是生育力和生殖成功的基础。生殖谱系的早期前体，即原始生殖细胞（PGC），在迁移到胚胎性腺的过程中在几个胚胎位置存活并增殖。通过阐明体内迁移 PGC 的活跃信号通路，我们能够创造重现这种胚胎生殖细胞环境的培养条件。在没有饲养细胞的特定培养基条件下，生长因子 FGF2、胰岛素和激活素 A 通过其同源信号通路发出信号，足以使具有种系能力的 PGC 进行自我更新。强制表达组成型活性 MEK1、AKT 和 SMAD3 蛋白可以取代它们各自的上游生长因子。出乎意料的是，我们发现BMP4可以在非克隆生长条件下替代Activin A。这些确定的培养基条件确定了 PGC 自我更新所需的关键分子途径，并将促进鸡遗传资源生物库和基因组编辑的工作。禽类原始生殖细胞的自我更新依赖于FGF2、胰岛素和激活素A分子BMP4可以在非克隆生长条件下替代激活素A确定的培养基条件将促进其他脊椎动物物种生殖细胞自我更新的研究在这篇文章中，McGrew及其同事定义了鸡原始生殖细胞自我更新所需的最小生长因子和信号通路。他们表明自我更新依赖于 FGF2、胰岛素和激活素 A 生长因子。在非克隆生长条件下，BMP4 可以替代激活素 A。这些确定的条件确定了 PGC 自我更新所需的关键分子途径。
Precise self-renewal of the germ cell lineage is fundamental to fertility and reproductive success. The early precursors for the germ lineage, primordial germ cells (PGCs), survive and proliferate in several embryonic locations during their migration to the embryonic gonad. By elucidating the active signaling pathways in migratory PGCs in vivo, we were able to create culture conditions that recapitulate this embryonic germ cell environment. In defined medium conditions without feeder cells, the growth factors FGF2, insulin, and Activin A, signaling through their cognate-signaling pathways, were sufficient for self-renewal of germline-competent PGCs. Forced expression of constitutively active MEK1, AKT, and SMAD3 proteins could replace their respective upstream growth factors. Unexpectedly, we found that BMP4 could replace Activin A in non-clonal growth conditions. These defined medium conditions identify the key molecular pathways required for PGC self-renewal and will facilitate efforts in biobanking of chicken genetic resources and genome editing. Avian primordial germ cell self-renewal is dependent on FGF2, insulin, and Activin A molecules BMP4 can replace Activin A in non-clonal growth conditions Defined culture medium conditions will facilitate studies of germ cell self-renewal in other vertebrate species In this article, McGrew and colleagues define the minimal growth factors and signaling pathways needed for the self-renewal of chicken primordial germ cells. They show that self-renewal is dependent on FGF2, insulin, and Activin A growth factors. BMP4 can replace Activin A in non-clonal growth conditions. These defined conditions identify the key molecular pathways required for PGC self-renewal.