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Adipocyte. 2018;7(2):96-105. doi: 10.1080/21623945.2018.1423911. Epub 2018 Feb 7.

Mirna biogenesis pathway is differentially regulated during adipose derived stromal/stem cell differentiation.

Author information

1
a Department for Biological and Agricultural Engineering , Louisiana State University , Baton Rouge , LA.
2
b Department of Regenerative Medicine , Naval Medical Research Center , Silver Spring , MD , USA.
3
h Center for Regenerative Medicine and Stem Cell Therapy, Tulane University School of Medicine , New Orleans , LA , USA.
4
i Department of Hematology/Oncology , Tulane University School of Medicine , New Orleans , LA , USA.
5
c Department of Orthopedics , Louisiana State University Health Science Center , New Orleans , LA , USA.
6
d Department of Molecular Virology , Immunology Medical & Genetics, Ohio State University , Columbus , OH , USA.
7
e Department of Surgery , Uniformed Services University of the Health Sciences-Walter Reed National Military Medical Center Bethesda , MD , USA.
8
f Departments of Medicine , Structural and Cellular Biology, & Surgery, Tulane University School of Medicine , New Orleans , LA , USA.
9
g LaCell LLC , New Orleans , LA , USA.

Abstract

Stromal/stem cell differentiation is controlled by a vast array of regulatory mechanisms. Included within these are methods of mRNA gene regulation that occur at the level of epigenetic, transcriptional, and/or posttranscriptional modifications. Current studies that evaluate the posttranscriptional regulation of mRNA demonstrate microRNAs (miRNAs) as key mediators of stem cell differentiation through the inhibition of mRNA translation. miRNA expression is enhanced during both adipogenic and osteogenic differentiation; however, the mechanism by which miRNA expression is altered during stem cell differentiation is less understood. Here we demonstrate for the first time that adipose-derived stromal/stem cells (ASCs) induced to an adipogenic or osteogenic lineage have differences in strand preference (-3p and -5p) for miRNAs originating from the same primary transcript. Furthermore, evaluation of miRNA expression in ASCs demonstrates alterations in both miRNA strand preference and 5'seed site heterogeneity. Additionally, we show that during stem cell differentiation there are alterations in expression of genes associated with the miRNA biogenesis pathway. Quantitative RT-PCR demonstrated changes in the Argonautes (AGO1-4), Drosha, and Dicer at intervals of ASC adipogenic and osteogenic differentiation compared to untreated ASCs. Specifically, we demonstrated altered expression of the AGOs occurring during both adipogenesis and osteogenesis, with osteogenesis increasing AGO1-4 expression and adipogenesis decreasing AGO1 gene and protein expression. These data demonstrate changes to components of the miRNA biogenesis pathway during stromal/stem cell differentiation. Identifying regulatory mechanisms for miRNA processing during ASC differentiation may lead to novel mechanisms for the manipulation of lineage differentiation of the ASC through the global regulation of miRNA as opposed to singular regulatory mechanisms.

KEYWORDS:

biogenesis; miRNA; stem cell differentiation

PMID:
29411671
PMCID:
PMC6152510
[Available on 2019-02-07]
DOI:
10.1080/21623945.2018.1423911

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