Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

Protein & Cell
Jinzhu XiangJianyong Han


It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a "dose effect". Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.


Dec 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·G R Martin
Jan 1, 1993·Methods in Enzymology·C L Stewart
Jan 1, 1993·Methods in Enzymology·R Ramírez-SolisA Bradley
Dec 4, 2003·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Guy S Eakin, Richard R Behringer
Oct 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Marcela Guzman-AyalaDaniel B Constam
Dec 14, 2004·Genesis : the Journal of Genetics and Development·Kristina VinterstenAndras Nagy
Feb 18, 2006·Nature Reviews. Genetics·Haibin Wang, Sudhansu K Dey
Dec 26, 2006·Nature Biotechnology·William T PoueymirouDavid M Valenzuela
Jun 19, 2009·Nature Reviews. Genetics·Magdalena Zernicka-GoetzAlexander W Bruce
Aug 13, 2009·Nature·Xiao-yang ZhaoQi Zhou
Apr 7, 2010·The Journal of Clinical Investigation·Katie Cockburn, Janet Rossant
Sep 10, 2014·PloS One·Yasuhide Ohinata, Tomoyuki Tsukiyama
Sep 24, 2014·Stem Cells and Development·Sabitri GhimirePetra De Sutter
Feb 12, 2015·Development·Siim Pauklin, Ludovic Vallier
Jun 28, 2016·Mechanisms of Development·Monika HumięckaAneta Suwińska

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