Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells

Ursula Nosi; Fredrik Lanner; Tsu Huang; Brian Cox

doi:10.1016/j.celrep.2017.04.040

Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells

Cell Rep. 2017 May 9;19(6):1101-1109. doi: 10.1016/j.celrep.2017.04.040.

Authors

Ursula Nosi¹, Fredrik Lanner², Tsu Huang¹, Brian Cox³

Affiliations

¹ Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
² Department of Clinical Science, Intervention and Technology, Karolinska Institute, 171 77 Solna, Sweden; Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, 141 86 Stockholm, Sweden.
³ Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: b.cox@utoronto.ca.

PMID: 28494860
DOI: 10.1016/j.celrep.2017.04.040

Abstract

The first cell fate choice of the preimplantation embryo generates the extraembryonic trophoblast and embryonic epiblast lineages. Embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) can be utilized to investigate molecular mechanisms of this first cell fate decision. It has been established that ESCs can be induced to acquire trophoblast lineage characteristics upon manipulation of lineage-determining transcription factors. Here, we have interrogated the potential of microRNAs (miRNAs) to drive trans-differentiation of ESCs into the trophoblast lineage. Analysis of gene expression data identified a network of TSC-enriched miRNAs that were predicted to target mRNAs enriched in ESCs. Ectopic expression of these miRNAs in ESCs resulted in a stable trophoblast phenotype, supported by gene expression changes and in vivo contribution potential. This process is highly miRNA-specific and dependent on Hdac2 inhibition. Our experimental evidence suggests that these miRNAs promote a mural trophectoderm (TE)-like cell fate with physiological properties that differentiate them from the polar TE.

Keywords: cell fate; embryo; embryonic stem cell; epigenetics; microRNA; microarray; mouse; reprogramming; trophectoderm; trophoblast stem cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Lineage*
Cells, Cultured
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / metabolism
Gene Expression Regulation, Developmental
Mice
MicroRNAs / genetics
MicroRNAs / metabolism*
Trophoblasts / cytology*
Trophoblasts / metabolism

Substances

MicroRNAs