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<p>The first embryonic cell differentiation in mice segregates the trophectoderm and the inner cell mass. Successful derivation of mouse trophoblast stem cells (TSCs) and trophectoderm stem cells (TESCs) has greatly facilitated the understanding of trophoblast differentiation. However, our understanding of early trophectoderm differentiation remains incomplete. Here we report the establishment of a morula-derived trophectoderm stem cell (MTSC) line from 32-cell embryos that show enhanced and uniform trophoblast core gene expression. Importantly, distinct from TSCs or TESCs, MTSCs represent a much earlier trophectoderm state (E3.5) than that of TSCs (E5.5–6.5) and TESCs (E4.5–5.5). MTSCs can robustly integrate into all cell lineages of the placenta. Moreover, MTSCs can self-organize to form placenta organoids. When partially differentiated MTSCs aggregate with embryonic stem cells, they form blastoids that efficiently implant uteruses. Finally, MSTC medium can efficiently convert embryonic stem cells, TSCs and TESCs into MTSC-like cells. Thus, MTSCs capture an early blastocyst trophectoderm state and provide a research model for studying trophoblast development.</p>

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Mouse trophectoderm stem cells generated with morula signalling inducers capture an early trophectoderm state

  • 期刊论文

  • 发表日期：

    2025年8月14日

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  • Yake Gao,
  • Mingying Li,
  • Wei Guan,
  • Wei Guo,
  • Shu Wei,
  • Fang Yan,
  • Wenrui Han,
  • Xueting Zhang,
  • Tong Yin,
  • Yunkun Dang,
  • Huanhuan Li,
  • José C. R. Silva,
  • Jian Zhang

摘要

The first embryonic cell differentiation in mice segregates the trophectoderm and the inner cell mass. Successful derivation of mouse trophoblast stem cells (TSCs) and trophectoderm stem cells (TESCs) has greatly facilitated the understanding of trophoblast differentiation. However, our understanding of early trophectoderm differentiation remains incomplete. Here we report the establishment of a morula-derived trophectoderm stem cell (MTSC) line from 32-cell embryos that show enhanced and uniform trophoblast core gene expression. Importantly, distinct from TSCs or TESCs, MTSCs represent a much earlier trophectoderm state (E3.5) than that of TSCs (E5.5–6.5) and TESCs (E4.5–5.5). MTSCs can robustly integrate into all cell lineages of the placenta. Moreover, MTSCs can self-organize to form placenta organoids. When partially differentiated MTSCs aggregate with embryonic stem cells, they form blastoids that efficiently implant uteruses. Finally, MSTC medium can efficiently convert embryonic stem cells, TSCs and TESCs into MTSC-like cells. Thus, MTSCs capture an early blastocyst trophectoderm state and provide a research model for studying trophoblast development.