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

ABSTRACT: 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.

SUBMITTER: Xiang J

PROVIDER: S-EPMC6053354 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Xiang Jinzhu J Cao Suying S Zhong Liang L Wang Hanning H Pei Yangli Y Wei Qingqing Q Wen Bingqiang B Mu Haiyuan H Zhang Shaopeng S Yue Liang L Yue Genhua G Lim Bing B Han Jianyong J

Protein & cell 20171012 8

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 f ...[more]

PMID: 29027123

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Project description:Introduction:The basement membrane (BM) is a sheet-like extracellular matrix (ECM) lining the basal side of epithelial and endothelial cells. The molecular composition of the BM diversifies as embryonic development proceeds, providing optimized microenvironments for individual cell types. In post-implantation stage embryos, the embryonic BMs are essential for differentiation of the epiblast, a layer of multipotent embryonic stem cells, and subsequent embryogenesis. To better understand the role of BMs and cell-BM interactions in early embryogenesis, it is imperative to accumulate information on the molecular entities of the embryonic BMs. Methods:We analyzed the expressions and localizations of 20 major BM proteins (11 laminin subunits, 6 type IV collagen subunits, nidogen-1 and -2, and perlecan) and other ECM-related proteins such as fibronectin and integrins in post-implantation stage embryos by immunohistochemistry. Results:We found that a set of BM proteins, laminin ?5, ?1, and ?1 (comprising laminin-511), type IV collagen ?1 and ?2 (yielding type IV collagen ?12?2 [IV]), nidogen-1 and -2, and perlecan, were consistently present in the epiblast/ectoderm BMs throughout the early post-implantation stages. In contrast, laminin ?1 was detected in the epiblast BM at E5.5 but decreased in later stages, suggesting that laminin-511 is a major laminin isoform in the early embryonic BM. In addition, fibronectin, a mesenchymal ECM protein, was enriched in the endoderm BM, indicating that the BM compositions differ between the ectoderm and the endoderm. Consistent with these observations, integrin ?5, a high-affinity receptor for fibronectin, was localized in the endoderm, while integrin ?6, a receptor for laminin-511, was localized in the ectoderm. Conclusions:The embryonic BMs underlying the epiblast/ectoderm contain a common toolkit comprising laminin-511, type IV collagen (?12?2 [IV]), nidogen-1 and -2, and perlecan, providing a physiological basis for the utility of laminin-511 as a culture substrate for pluripotent stem cells. The distinctive association of laminin-511 and fibronectin with endodermal and ectodermal cells, together with the differential expression of integrin ?5 and ?6 in these cells, suggests that the ectodermal and endodermal cells rely on their integrin-dependent interactions with laminin-511 and fibronectin, respectively, to ensure their fate specification in embryonic development.

Dataset Information

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

Publications

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

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