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.

Author contributions

Conceptualization: F.S., L.C.L., M.M.P.; Methodology: F.S., D.P., A.W., M.M.-Z.; Validation: F.S., D.P., O.F., A.W.; Formal analysis: F.S., M.K., C.T., L.C.L.; Investigation: F.S., D.P., A.W.; Resources: F.S., D.P., K.A.N.R., K.K.N., C.-W.C., M.M.-Z., D.R.N.; Writing - original draft: F.S.; Writing - review & editing: M.K., A.W., C.-W.C., L.C.L., M.M.P.; Visualization: F.S., M.M.P.; Supervision: D.R.N., L.C.L., M.M.P.; Funding acquisition: M.M.P.

Funding

This work was supported by the National Institute of Child Health and Human Development (R01-NIH HD07110 to M.M.P.). M.M.P. and L.C.L. were also supported by a grant from the California Institute for Regenerative Medicine (RN3-06396 to M.M.P.). Deposited in PMC for release after 12 months.

Data availability

Microarray data have been deposited in the Gene Expression Omnibus (GEO) database under accession numbers GSE100053, GSE100052, GSE100051, GSE127824 and GSE100279.

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