Nucleoporin insufficiency disrupts a pluripotent regulatory circuit in a pro-arrhythmogenic stem cell line.

TitleNucleoporin insufficiency disrupts a pluripotent regulatory circuit in a pro-arrhythmogenic stem cell line.
Publication TypeJournal Article
Year of Publication2019
AuthorsPreston, CC, Storm, EC, Burdine, RD, Bradley, TA, Uttecht, AD, Faustino, RS
JournalSci Rep
Volume9
Issue1
Pagination12691
Date Published2019 Sep 03
ISSN2045-2322
Abstract

Nucleoporins have been reported to regulate pluripotent biology, but how they do so remains partially characterized. This study examined the effects of nup155 gene disruption on mouse embryonic stem cells to gain insights into possible mechanisms by which nucleoporins regulate pluripotency in a pro-arrhythmogenic stem cell line. Embryonic stem cells with gene-trapped nup155 exhibited aberrant colony morphology underscored by abnormal transcriptome remodeling. Bioinformatic analysis of whole transcriptome data from nup155+/- embryonic stem cells revealed changes in a variety of non-coding RNA elements, with significant under expression of miR291a, miR291b, miR293, and miR294. These miRNAs are members of the larger regulatory miR290-295 cluster that regulates pluripotency and are controlled by the canonical stem cell-related factors SOX2, OCT4, and NANOG. Expression analysis of these factors revealed downregulation in all three, supported by biochemical profiling and image analysis. These data implicate disruption of the miR-SOX2/OCT4/NANOG regulatory circuit occurs downstream of nup155 gene lesion.

DOI10.1038/s41598-019-49147-4
Alternate JournalSci Rep
PubMed ID31481660
PubMed Central IDPMC6722237
Grant ListP20 GM103620 / GM / NIGMS NIH HHS / United States
P20GM103620 / / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) /
14SDG20380322 / / American Heart Association (American Heart Association, Inc.) /