Cellular systems biology identifies dynamic trophoblast populations in early human placentas

ABSTRACT: To address early human placenta development, we aimed to characterize the cell surface proteomic profile of early trophoblast cells in an effort to understand trophoblast heterogeneity and population dynamics. We quantify cell surface protein expression in early first trimester human placentas using a high throughput flow cytometry screen of 370 Cluster of Differentiation (CD) antigens and confidently identified 23 increasing and 13 decreasing markers of dynamic populations between weeks 6 and 10 of human placenta development. We were particularly interested in transient trophoblast populations expressing either EpCAM (CD326) or CDCP1 (CD318) populations of trophoblasts. Immunohistochemistry analysis revealed these CD antigens are expressed by discrete cells with EpCAM localized to trophoblast in the proximal villi columns while CDCP1 is expressed by cells in the distal columns. Multi-color flow analysis confirmed independence of CDCP1 and EPCAM expressing cell populations and identified EpCAM cells as positive for EGFR. Microarray analysis of gene expression indicated EpCAM+/EGFR+ and EGFR+ cells showed high degree of gene expression similarities to villus cytotrophbolast but that loss of EpCAM expression was concomitant with exit from the cell cycle as EpCAM/EGFR cell were mitotically active while CDCP1 positive trophoblast are enriched in gene sets related to immune regulation functions and cell cycle/cell division and have significant similar gene expression to extravillous cytotrophoblast. Our study indicates at least two distinct subpopulations of cytotrophoblasts exit in the early first trimester and that the column likely maintains pools of actively dividing progenitor cells giving rise to the developing placenta villus tree.

ORGANISM(S): Homo sapiens

PROVIDER: GSE90646 | GEO | 2019/02/01

REPOSITORIES: GEO