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Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation.
Schira-Heinen, Jessica Czapla, Agathe Hendricks, Marion Kloetgen, Andreas Wruck, Wasco Adjaye, James Kögler, Gesine Werner Müller, Hans Stühler, Kai Trompeter, Hans-Ingo
Schira-Heinen, Jessica
Czapla, Agathe
Hendricks, Marion
Kloetgen, Andreas
Wruck, Wasco
Adjaye, James
Kögler, Gesine
Werner Müller, Hans
Stühler, Kai
Trompeter, Hans-Ingo
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2020-02-24
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Abstract
The contribution of microRNA-mediated posttranscriptional regulation on the final proteome in differentiating cells remains elusive. Here, we evaluated the impact of microRNAs (miRNAs) on the proteome of human umbilical cord blood-derived unrestricted somatic stem cells (USSC) during retinoic acid (RA) differentiation by a systemic approach using next generation sequencing analysing mRNA and miRNA expression and quantitative mass spectrometry-based proteome analyses. Interestingly, regulation of mRNAs and their dedicated proteins highly correlated during RA-incubation. Additionally, RA-induced USSC demonstrated a clear separation from native USSC thereby shifting from a proliferating to a metabolic phenotype. Bioinformatic integration of up- and downregulated miRNAs and proteins initially implied a strong impact of the miRNome on the XXL-USSC proteome. However, quantitative proteome analysis of the miRNA contribution on the final proteome after ectopic overexpression of downregulated miR-27a-5p and miR-221-5p or inhibition of upregulated miR-34a-5p, respectively, followed by RA-induction revealed only minor proportions of differentially abundant proteins. In addition, only small overlaps of these regulated proteins with inversely abundant proteins in non-transfected RA-treated USSC were observed. Hence, mRNA transcription rather than miRNA-mediated regulation is the driving force for protein regulation upon RA-incubation, strongly suggesting that miRNAs are fine-tuning regulators rather than active primary switches during RA-induction of USSC.
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Sci Rep. 2020 Feb 24;10(1):3284. doi: 10.1038/s41598-020-60065-8.
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en
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2045-2322
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Attribution-NonCommercial-ShareAlike 4.0 International