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作者

Xinyi Jia, Bing Peng, Hongjin Zhao, Chunhui Wang, Aibin He, Wei Tao, Peng Du

作者单位

Affiliations ¹ MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, China. ² Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China. ³ Institute of Molecular Medicine and National Biomedical Imaging Center, College of Future Technology, Peking-Tsinghua Center for Life Sciences and State Key Laboratory of Gene Function and Modulation Research, Peking University, Beijing, 100871, China. ⁴ Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. ⁵ Beijing Advanced Center of RNA Biology, Peking University, Beijing, 100871, China.

刊名

Protein & cell

年份

2025

页码

pwaf098

ISSN

1674-8018

关键词

embryonic development epigenetic organoid placenta pregnancy stem cell totipotency transcriptomic trophectoderm trophoblast.

摘要

The trophectoderm produced from totipotent blastomeres initiates trophoblast development, while placental deficiencies can cause pregnancy disorders. Yet, a culture system that fully recapitulates the entire placenta development is still lacking, greatly limiting related studies. Here, we captured mouse trophectoderm-like stem cells , which can give rise to all trophoblast lineages and be applied to generate trophoblast organoids. We achieved the induction and maintenance of TELSCs from totipote...更多

The trophectoderm produced from totipotent blastomeres initiates trophoblast development, while placental deficiencies can cause pregnancy disorders. Yet, a culture system that fully recapitulates the entire placenta development is still lacking, greatly limiting related studies. Here, we captured mouse trophectoderm-like stem cells , which can give rise to all trophoblast lineages and be applied to generate trophoblast organoids. We achieved the induction and maintenance of TELSCs from totipotent blastomere-like stem cells or early embryos through a Hippo-YAP/Notch-to-TGFβ1 signaling switch. At the molecular level, TELSCs resemble E4.5 trophectoderm and are distinct from all previously known trophoblast-like stem cells. Functionally, TELSCs can generate all trophoblast lineages in both teratoma and chimera assays. We further applied TELSCs to generate trophoblast organoids containing various mature trophoblasts and a self-renewing extraembryonic ectoderm -like progenitor population. Interestingly, we observed transiently formed rosette-like structures that rely on Itgb1, which are essential to induce ExE-like progenitors and to generate organoids eventually. Thus, the capture of TELSCs enables comprehensive insights into placental development.收起

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