Comparison of syncytiotrophoblast generated from human embryonic stem cells and from term placentas.

Journal Article (Journal Article)

Human embryonic stem cells (ESCs) readily commit to the trophoblast lineage after exposure to bone morphogenetic protein-4 (BMP-4) and two small compounds, an activin A signaling inhibitor and a FGF2 signaling inhibitor (BMP4/A83-01/PD173074; BAP treatment). During differentiation, areas emerge within the colonies with the biochemical and morphological features of syncytiotrophoblast (STB). Relatively pure fractions of mononucleated cytotrophoblast (CTB) and larger syncytial sheets displaying the expected markers of STB can be obtained by differential filtration of dispersed colonies through nylon strainers. RNA-seq analysis of these fractions has allowed them to be compared with cytotrophoblasts isolated from term placentas before and after such cells had formed syncytia. Although it is clear from extensive gene marker analysis that both ESC- and placenta-derived syncytial cells are trophoblast, each with the potential to transport a wide range of solutes and synthesize placental hormones, their transcriptome profiles are sufficiently dissimilar to suggest that the two cell types have distinct pedigrees and represent functionally different kinds of STB. We propose that the STB generated from human ESCs represents the primitive syncytium encountered in early pregnancy soon after the human trophoblast invades into the uterine wall.

Full Text

Duke Authors

Cited Authors

  • Yabe, S; Alexenko, AP; Amita, M; Yang, Y; Schust, DJ; Sadovsky, Y; Ezashi, T; Roberts, RM

Published Date

  • May 10, 2016

Published In

Volume / Issue

  • 113 / 19

Start / End Page

  • E2598 - E2607

PubMed ID

  • 27051068

Pubmed Central ID

  • PMC4868474

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1601630113

Language

  • eng

Conference Location

  • United States