Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development

对妊娠期间小鼠和人类胎盘的比较分析揭示了胎盘发育的物种特异性调节剂

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作者:Francesca Soncin, Marwa Khater, Cuong To, Donald Pizzo, Omar Farah, Anna Wakeland, Kanaga Arul Nambi Rajan, Katharine K Nelson, Ching-Wen Chang, Matteo Moretto-Zita, David R Natale, Louise C Laurent, Mana M Parast

Abstract

An increasing body of evidence points to significant spatio-temporal differences in early placental development between mouse and human, but a detailed comparison of placentae in these two species is missing. We set out to compare placentae from both species across gestation, with a focus on trophoblast progenitor markers. We found that CDX2 and ELF5, but not EOMES, are expressed in early post-implantation trophoblast subpopulations in both species. Genome-wide expression profiling of mouse and human placentae revealed clusters of genes with distinct co-expression patterns across gestation. Overall, there was a closer fit between patterns observed in the placentae when the inter-species comparison was restricted to human placentae through gestational week 16 (thus, excluding full-term samples), suggesting that the developmental timeline in mouse runs parallel to the first half of human placental development. In addition, we identified VGLL1 as a human-specific marker of proliferative cytotrophoblast, where it is co-expressed with the transcription factor TEAD4. As TEAD4 is involved in trophectoderm specification in the mouse, we posit a regulatory role for VGLL1 in early events during human placental development.

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