| RRC ID |
86309
|
| 著者 |
Shimizu T, Oike A, Kobayashi EH, Sekiya A, Kobayashi N, Shibata S, Hamada H, Saito M, Yaegashi N, Suyama M, Arima T, Okae H.
|
| タイトル |
CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.
|
| 巻・号 |
120(51)
|
| ページ |
e2311372120
|
| 公開日 |
2023-12-19
|
| DOI |
10.1073/pnas.2311372120
|
| PMID |
38085778
|
| PMC |
PMC10742386
|
| MeSH |
Animals
Cell Differentiation
Clustered Regularly Interspaced Short Palindromic Repeats
Female
Humans
Mammals
Mice
Placenta*
Placentation* / genetics
Pregnancy
Stem Cells
Trophoblasts
|
| IF |
9.412
|
| リソース情報 |
| 遺伝子材料 |
pCAG-HIVgp (RDB04394)
pCS-hU6-Neo(V2) (RDB21099) |
