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首页> 美国卫生研究院文献>Protein Cell >Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos
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Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

机译：多能干细胞在注入受体胚胎后会分泌激活素A以提高其上皮细胞能力

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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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-017-0470-y) contains supplementary material, which is available to authorized users.
机译：与囊胚注射相比，为什么将多能干细胞（PSC）注射入4细胞或8细胞阶段胚胎中产生的嵌合体，对嵌合体的贡献更大，目前尚不清楚。在这里，我们表明，不仅胚胎干细胞（ESC），而且诱导的多能干细胞（iPSC）均可通过4细胞阶段胚胎注射生成F0接近100％供体细胞的小鼠，这种方法具有“剂量效应” 。通过对PSC分泌蛋白的分析，发现激活素A可以阻止上皮层（EPI）谱系发育，同时促进滋养外胚层（TE）分化，从而用PSC取代宿主胚胎的EPI谱系。有趣的是，将ESCs注射到用激活素A培养的胚泡中（从4细胞阶段到胚泡早期在E3.5培养）可以增加ESC对嵌合体的贡献。结果表明，PSC通过影响小鼠早期胚胎的发育，可在注射入受体胚胎后分泌蛋白Activin A，从而提高其EPI能力。此结果对于优化嵌合体生产系统和深入了解PSC对早期胚胎发育的影响很有用。电子补充材料本文的在线版本（doi：10.1007 / s13238-017-0470-y）包含补充材料，该材料是可供授权用户使用。

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