Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation

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 retino...

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Autores principales:	Jessica Schira-Heinen, Agathe Czapla, Marion Hendricks, Andreas Kloetgen, Wasco Wruck, James Adjaye, Gesine Kögler, Hans Werner Müller, Kai Stühler, Hans-Ingo Trompeter
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/62dae02cb5f54e3cbd426e26e69c88eb
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spelling	oai:doaj.org-article:62dae02cb5f54e3cbd426e26e69c88eb2021-12-02T11:02:17ZFunctional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation10.1038/s41598-020-60065-82045-2322https://doaj.org/article/62dae02cb5f54e3cbd426e26e69c88eb2020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-60065-8https://doaj.org/toc/2045-2322Abstract 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.Jessica Schira-HeinenAgathe CzaplaMarion HendricksAndreas KloetgenWasco WruckJames AdjayeGesine KöglerHans Werner MüllerKai StühlerHans-Ingo TrompeterNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jessica Schira-Heinen Agathe Czapla Marion Hendricks Andreas Kloetgen Wasco Wruck James Adjaye Gesine Kögler Hans Werner Müller Kai Stühler Hans-Ingo Trompeter Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
description	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.
format	article
author	Jessica Schira-Heinen Agathe Czapla Marion Hendricks Andreas Kloetgen Wasco Wruck James Adjaye Gesine Kögler Hans Werner Müller Kai Stühler Hans-Ingo Trompeter
author_facet	Jessica Schira-Heinen Agathe Czapla Marion Hendricks Andreas Kloetgen Wasco Wruck James Adjaye Gesine Kögler Hans Werner Müller Kai Stühler Hans-Ingo Trompeter
author_sort	Jessica Schira-Heinen
title	Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
title_short	Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
title_full	Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
title_fullStr	Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
title_full_unstemmed	Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation
title_sort	functional omics analyses reveal only minor effects of micrornas on human somatic stem cell differentiation
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/62dae02cb5f54e3cbd426e26e69c88eb
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Functional omics analyses reveal only minor effects of microRNAs on human somatic stem cell differentiation

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