生物
诱导多能干细胞
Wnt信号通路
生殖系
细胞生物学
胚胎干细胞
转录因子
外胚层
干细胞
中胚层
生殖细胞
细胞分化
遗传学
信号转导
基因
原肠化
作者
Yôji Kojima,Kotaro Sasaki,Shihori Yokobayashi,Yoshitake Sakai,Tomonori Nakamura,Yukihiro Yabuta,Fumio Nakaki,So Nagaoka,Knut Woltjen,Akitsu Hotta,Takuya Yamamoto,Mitinori Saitou
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2017-10-01
卷期号:21 (4): 517-532.e5
被引量:149
标识
DOI:10.1016/j.stem.2017.09.005
摘要
Germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. This process can be modeled with human induced pluripotent stem cells (hiPSCs) by differentiating them into primordial germ cell-like cells (hPGCLCs) through an incipient mesoderm-like cell (iMeLC) state. Here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hPGCLC differentiation from iPSCs. Germline competence of iMeLCs is dictated by the duration and dosage of WNT signaling, which induces expression of EOMES to activate SOX17, a key driver of hPGCLC specification. Upon hPGCLC induction, BMP signaling activates TFAP2C in a SOX17-independent manner. SOX17 and TFAP2C then cooperatively instate an hPGCLC transcriptional program, including BLIMP1 expression. This specification program diverges from its mouse counterpart regarding key transcription factors and their hierarchies, and it provides a foundation for further study of human germ cell development.
科研通智能强力驱动
Strongly Powered by AbleSci AI