論文

査読有り 国際誌
2017年10月5日

Evolutionarily Distinctive Transcriptional and Signaling Programs Drive Human Germ Cell Lineage Specification from Pluripotent Stem Cells.

Cell stem cell
  • Yoji Kojima
  • ,
  • Kotaro Sasaki
  • ,
  • Shihori Yokobayashi
  • ,
  • Yoshitake Sakai
  • ,
  • Tomonori Nakamura
  • ,
  • Yukihiro Yabuta
  • ,
  • Fumio Nakaki
  • ,
  • So Nagaoka
  • ,
  • Knut Woltjen
  • ,
  • Akitsu Hotta
  • ,
  • Takuya Yamamoto
  • ,
  • Mitinori Saitou

21
4
開始ページ
517
終了ページ
532
記述言語
英語
掲載種別
DOI
10.1016/j.stem.2017.09.005

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.

リンク情報
DOI
https://doi.org/10.1016/j.stem.2017.09.005
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28985527
ID情報
  • DOI : 10.1016/j.stem.2017.09.005
  • PubMed ID : 28985527

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