Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells

Abstract

Highlights d Reprogramming of patient somatic cells to induced hTSCs with OSKM d Conversion of naive and extended hPSCs to hTSCs d Comparison of models of the human trophoblast lineage d h(i/c)TSCs are akin to day 8 trophoblasts of the human embryo

Chemically defined and xeno-free culture condition for human extended pluripotent stem cells

“…4b ). This observation was consistent with one recent report showing successful conversion of feeder-cultured hEPS cells into human trophoblast stem cells in vitro 25 . The expanded developmental potentials of xeno-free hEPS cells were further supported by their contribution to both embryonic and extraembryonic lineages in E4.5 and E6.5 mouse embryos (Fig.…”

Opportunities and challenges with stem cell-based embryo models

“…Several pieces of evidence suggest that hESCs themselves may have more potential to generate trophectoderm than their mouse equivalents, beginning with early evidence of trophoblast gene expression in hES cultures ( Xu et al., 2002 ). Recently several groups have shown that human naive ESCs have the potential to generate TS-like cells in vitro ( Castel et al., 2020 ; Cinkornpumin et al., 2020 ; Dong et al., 2020 ; Guo et al., 2020 ). Furthermore, it has been shown that the pathway to reprogramming human fibroblasts to iPSC may pass through a window where trophectoderm-like gene expression can be discerned and TS-like cells can be isolated ( Liu et al., 2020 ).…”

All models are wrong, but some are useful: Establishing standards for stem cell-based embryo models

“…Subsequently, similar results were achieved by converting hESCs into either CDX2 - positive trophectoderm stem cells or CDX2-negative TSCs ( Mischler et al, 2019 ). Several reports have also now shown that adult cells can be reprogrammed directly into TSCs resembling the cytotrophoblast of the postimplantation embryo ( Castel et al, 2020 ; Liu et al, 2020 ). Other researchers argue that only naive hESCs retain the trophectoderm lineage potential ( Cinkornpumin et al, 2020 ; Dong et al, 2020 ; Guo et al, 2020 ; Io et al, 2020 ).…”

“…Exactly how they relate to human naive and primed ESCs, both of which have been shown to exhibit extraembryonic differentiation, has not been definitively established. However, recent transcriptional analyses suggest extended pluripotent human stem cells most closely resemble primed human ESCs ( Castel et al, 2020 ; Striparo et al., 2018 ).…”