A transcriptomic comparison of in vitro models of the human placenta

Introduction: Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. The aim of this research was to compare the transcriptomes of common in vitro models of the human placenta compared to bulk human placental tissue.

Methods: We performed differential gene expression analysis on publicly available transcriptomic data from 7 in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, Villous Explants, and Trophoblast Stem Cells) and compared to bulk placental tissue from 2 cohort studies (CANDLE and GAPPS) or individual trophoblast cell types derived from bulk placental tissue.

Results: All in vitro placental models had a substantial number of differentially expressed genes (DEGs, FDR<0.01) compared to the CANDLE and GAPPS placentas (Average DEGs = 10,624), and the individual trophoblast cell types (Average DEGs = 5413), indicating that there are vast differences in gene expression. Hierarchical clustering identified 54 gene clusters with distinct expression profiles across placental models, with 23 clusters enriched for specific KEGG pathways. Placental cell lines were classified by fetal sex based on expression of Y-chromosome genes that identified HTR-8/SVneo cells as female origin, while JEG-3, JAR, and BeWo cells are of male origin.

Discussion: None of the models were a close approximation of the human bulk placental transcriptome, highlighting the challenges with model selection. To enable appropriate model selection, we adapted our data into a web application: "Comparative Transcriptomic Placental Model Atlas (CTPMA)".