Specification of Trophoblast from Embryonic Stem Cells Exposed to BMP4

Overview

Journal Biol Reprod

Publisher Oxford University Press

Specialty Reproductive Medicine

Date 2018 Mar 27

PMID 29579154

Citations 38

Authors

R Michael Roberts

Toshihiko Ezashi

Megan A Sheridan

Ying Yang

Affiliations

Soon will be listed here.

Abstract

Trophoblast (TB) comprises the outer cell layers of the mammalian placenta that make direct contact with the maternal uterus and, in species with a highly invasive placenta, maternal blood. It has its origin as trophectoderm, a single epithelial layer of extra-embryonic ectoderm that surrounds the embryo proper at the blastocyst stage of development. Here, we briefly compare the features of TB specification and determination in the mouse and the human. We then review research on a model system that has been increasingly employed to study TB emergence, namely the BMP4 (bone morphogenetic protein-4)-directed differentiation of human embryonic stem cells (ESCd), and discuss why outcomes using it have proved so uneven. We also examine the controversial aspects of this model, particularly the issue of whether or not the ESCd represents TB at all. Our focus here has been to explore similarities and potential differences between the phenotypes of ESCd, trophectoderm, placental villous TB, and human TB stem cells. We then explore the role of BMP4 in the differentiation of human pluripotent cells to TB and suggest that it converts the ESC into a totipotent state that is primed for TB differentiation when self-renewal is blocked. Finally we speculate that the TB formed from ESC is homologous to the trophectoderm-derived, invasive TB that envelopes the implanting conceptus during the second week of pregnancy.

Citing Articles

Generation of Bona Fide Human Induced Trophoblast Stem Cells by Direct Reprogramming of Term Umbilical Cord Cells.

van Voorden A, Boussata S, Keijser R, Vermij M, Wagner M, Ganzevoort W Int J Mol Sci. 2025; 26(1.

PMID: 39796127 PMC: 11719488. DOI: 10.3390/ijms26010271.

Small and Long Non-Coding RNA Analysis for Human Trophoblast-Derived Extracellular Vesicles and Their Effect on the Transcriptome Profile of Human Neural Progenitor Cells.

Kinkade J, Singh P, Verma M, Khan T, Ezashi T, Bivens N Cells. 2024; 13(22).

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Chimerization of human ESC-derived extraembryonic cells with the mouse blastocyst.

Fu S, Huang B, Li E, Xu X, Xu R Int J Biol Sci. 2024; 20(13):5056-5069.

PMID: 39430245 PMC: 11488584. DOI: 10.7150/ijbs.99519.

Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells.

Balestrini P, Abdelbaki A, McCarthy A, Devito L, Senner C, Chen A Development. 2024; 151(17).

PMID: 39250534 PMC: 11556314. DOI: 10.1242/dev.202778.

Bioengineering-tissue strategies to model mammalian implantation .

Pennarossa G, Arcuri S, Zmijewska A, Orini E, Gandolfi F, Brevini T Front Bioeng Biotechnol. 2024; 12:1430235.

PMID: 39132254 PMC: 11310004. DOI: 10.3389/fbioe.2024.1430235.

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