Translator Disclaimer
4 September 2013 Role of LIN28A in Mouse and Human Trophoblast Cell Differentiation
Jill L. Seabrook, Jeremy D. Cantlon, Austin J. Cooney, Erin E. McWhorter, Brittany A. Fromme, Gerrit J. Bouma, Russell V. Anthony, Quinton A. Winger
Author Affiliations +
Abstract

Proper regulation of trophoblast proliferation, differentiation, and function are critical for placenta development and function. The RNA-binding protein, LIN28A, has been well characterized as a potent regulator of differentiation in embryonic stem cells; however, little is known about the function of LIN28A in the placenta. We assessed LIN28A in vitro using mouse trophoblast stem (mTS) cells and human trophoblast cells (ACH-3P). We observed that LIN28A decreased and let-7 miRNA increased when mTS cells were induced to differentiate into mouse trophoblast giant cells (mTGCs) upon the removal of FGF4, heparin and conditioned medium. Similarly, we observed that LIN28A decreased in ACH-3P cells induced to syncytialize with forskolin treatment. To assess LIN28A in vivo we examined Embryonic Day 11.5 mouse placenta and observed abundant LIN28A in the chorioallantoic interface and labyrinth layer, with little LIN28A staining in spongiotrophoblast or differentiated mTGCs. Additionally, shRNA-mediated LIN28A knockdown in ACH-3P cells resulted in increased spontaneous syncytialization, and increased levels of syncytiotrophoblast markers hCG, LGALS13, and ERVW-1 mRNA. Additionally, targeted degradation of LIN28A mRNA increased responsiveness to forskolin-induced differentiation. In contrast, targeted degradation of Lin28a mRNA in mTS cells did not alter cell phenotype when maintained under proliferative culture conditions. Together, these data establish that LIN28A has a functional role in regulating trophoblast differentiation and function, and that loss of LIN28A in human trophoblast is sufficient to induce differentiation, but does not induce differentiation in the mouse.

Jill L. Seabrook, Jeremy D. Cantlon, Austin J. Cooney, Erin E. McWhorter, Brittany A. Fromme, Gerrit J. Bouma, Russell V. Anthony, and Quinton A. Winger "Role of LIN28A in Mouse and Human Trophoblast Cell Differentiation," Biology of Reproduction 89(4), (4 September 2013). https://doi.org/10.1095/biolreprod.113.109868
Received: 5 April 2013; Accepted: 1 August 2013; Published: 4 September 2013
JOURNAL ARTICLE
PAGES

This article is only available to subscribers.
It is not available for individual sale.
+ SAVE TO MY LIBRARY

SHARE
ARTICLE IMPACT
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top