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Capturing human trophoblast development with naive pluripotent stem cells in vitro. | LitMetric

AI Article Synopsis

  • Trophoblasts are crucial for pregnancy and develop from embryonic cells called trophectoderm, differentiating into various types that form the placenta.
  • This study shows that naïve human pluripotent stem cells (PSCs) can effectively mimic the development of trophoblasts, creating cells that demonstrate characteristics of both transitional and proliferating trophoblasts.
  • In contrast, primed PSCs produce trophoblast-like cells that differ from naïve PSC-derived cells, suggesting a unique and valuable model for understanding trophoblast development and related health issues.

Article Abstract

Trophoblasts are extraembryonic cells that are essential for maintaining pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs), composing the placenta. Here we show that naïve, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naive PSC-derived TE and CTs (nCTs) recreated human and monkey TE-to-CT transition. nCTs self-renewed as CT stem cells and had the characteristics of proliferating villous CTs and CTs in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (BMP4, A83-01, and PD173074 [BAP]-treated primed PSCs [pBAPs]), pBAPs were distinct from nCTs and human placenta-derived CT stem cells, exhibiting properties consistent with the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naive human PSCs. Our system provides a platform to study the molecular mechanisms underlying trophoblast development and related diseases.

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Source
http://dx.doi.org/10.1016/j.stem.2021.03.013DOI Listing

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