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

Publication date: 9 May 2017
Source:Cell Reports, Volume 19, Issue 6
Author(s): Ursula Nosi, Fredrik Lanner, Tsu Huang, Brian Cox
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.

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Teaser

Nosi et al. identify microRNAs sufficient to drive embryonic to extraembryonic lineage conversion by employing stem cell models. Trophoblast-enriched microRNAs downregulate pluripotency-associated genes in ESCs and drive the acquisition of a preimplantation mural trophectoderm phenotype. This work suggests the involvement of microRNAs in networks regulating preimplantation development.


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