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

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, and Mana M. Parast

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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