Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos.
Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos.
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多能干细胞注射到受体胚胎后，会分泌激活素 A 以提高其外胚层能力。
DOI：
10.1007/s13238-017-0470-y
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发表时间：
2018-08
期刊：
影响因子：
21.1
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Xiang J;Cao S;Zhong L;Wang H;Pei Y;Wei Q;Wen B;Mu H;Zhang S;Yue L;Yue G;Lim B;Han J
将多能干细胞注射到4-细胞期或8-细胞期胚胎中产生的嵌合体比注入囊胚产生的嵌合体贡献更大的原因尚不完全清楚。在这里，我们证明了不仅胚胎干细胞(ESCs)，而且诱导多能干细胞(IPSCs)可以通过4-细胞期胚胎注射产生F0几乎100%的供体细胞来源的小鼠，并且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阻碍了外胚层(EPI)谱系的发育，而促进了滋养外胚层(TE)的分化，导致宿主胚胎的EPI谱系被PSCs取代。有趣的是，将ESCs注射到用激活素A培养的囊胚中(从4-细胞期培养到E3.5的早期囊胚)，可以增加ESCs对嵌合体的贡献。结果表明，PSCs通过分泌激活素A蛋白，通过影响小鼠早期胚胎的发育来提高其在受体胚胎中的EPI能力。这一结果对于优化嵌合体生产系统和深入了解PSCs对早期胚胎发育的影响是有用的。
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.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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影响因子：
12.3
作者：
Fan X;Zhang X;Wu X;Guo H;Hu Y;Tang F;Huang Y
通讯作者：
Huang Y