RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat

Abstract MicroRNAs are small (~ 22nt long) noncoding RNAs (ncRNAs) that regulate gene expression at the post-transcriptional level. Over 2000 microRNAs have been described in humans and many are implicated in human pathologies including tissue fibrosis. Hepatic stellate cells (HSC) are the major cel...

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Autores principales: Laura Sabater, Luigi Locatelli, Fiona Oakley, Timothy Hardy, Jeremy French, Stuart M. Robinson, Gourab Sen, D. A. Mann, Jelena Mann
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Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/8f906b3b042a46b4911aff0dbd9c06a0
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spelling oai:doaj.org-article:8f906b3b042a46b4911aff0dbd9c06a02021-12-02T16:18:07ZRNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat10.1038/s41598-020-78776-32045-2322https://doaj.org/article/8f906b3b042a46b4911aff0dbd9c06a02020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78776-3https://doaj.org/toc/2045-2322Abstract MicroRNAs are small (~ 22nt long) noncoding RNAs (ncRNAs) that regulate gene expression at the post-transcriptional level. Over 2000 microRNAs have been described in humans and many are implicated in human pathologies including tissue fibrosis. Hepatic stellate cells (HSC) are the major cellular contributors to excess extracellular matrix deposition in the diseased liver and as such are important in the progression of liver fibrosis. We employed next generation sequencing to map alterations in the expression of microRNAs occurring across a detailed time course of culture-induced transdifferentiation of primary human HSC, this a key event in fibrogenesis. Furthermore, we compared profiling of human HSC microRNAs with that of rat HSC so as to identify those molecules that are conserved with respect to modulation of expression. Our analysis reveals that a total of 229 human microRNAs display altered expression as a consequence of HSC transdifferentiation and of these 104 were modulated early during the initiation phase. Typically modulated microRNAs were targeting kinases, transcription factors, chromatin factors, cell cycle regulators and growth factors. 162 microRNAs changed in expression during transdifferentiation of rat HSC, however only 17 underwent changes that were conserved in human HSC. Our study therefore identifies widespread changes in the expression of HSC microRNAs in fibrogenesis, but suggests a need for caution when translating data obtained from rodent HSC to events occurring in human cells.Laura SabaterLuigi LocatelliFiona OakleyTimothy HardyJeremy FrenchStuart M. RobinsonGourab SenD. A. MannJelena MannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Laura Sabater
Luigi Locatelli
Fiona Oakley
Timothy Hardy
Jeremy French
Stuart M. Robinson
Gourab Sen
D. A. Mann
Jelena Mann
RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat
description Abstract MicroRNAs are small (~ 22nt long) noncoding RNAs (ncRNAs) that regulate gene expression at the post-transcriptional level. Over 2000 microRNAs have been described in humans and many are implicated in human pathologies including tissue fibrosis. Hepatic stellate cells (HSC) are the major cellular contributors to excess extracellular matrix deposition in the diseased liver and as such are important in the progression of liver fibrosis. We employed next generation sequencing to map alterations in the expression of microRNAs occurring across a detailed time course of culture-induced transdifferentiation of primary human HSC, this a key event in fibrogenesis. Furthermore, we compared profiling of human HSC microRNAs with that of rat HSC so as to identify those molecules that are conserved with respect to modulation of expression. Our analysis reveals that a total of 229 human microRNAs display altered expression as a consequence of HSC transdifferentiation and of these 104 were modulated early during the initiation phase. Typically modulated microRNAs were targeting kinases, transcription factors, chromatin factors, cell cycle regulators and growth factors. 162 microRNAs changed in expression during transdifferentiation of rat HSC, however only 17 underwent changes that were conserved in human HSC. Our study therefore identifies widespread changes in the expression of HSC microRNAs in fibrogenesis, but suggests a need for caution when translating data obtained from rodent HSC to events occurring in human cells.
format article
author Laura Sabater
Luigi Locatelli
Fiona Oakley
Timothy Hardy
Jeremy French
Stuart M. Robinson
Gourab Sen
D. A. Mann
Jelena Mann
author_facet Laura Sabater
Luigi Locatelli
Fiona Oakley
Timothy Hardy
Jeremy French
Stuart M. Robinson
Gourab Sen
D. A. Mann
Jelena Mann
author_sort Laura Sabater
title RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat
title_short RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat
title_full RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat
title_fullStr RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat
title_full_unstemmed RNA sequencing reveals changes in the microRNAome of transdifferentiating hepatic stellate cells that are conserved between human and rat
title_sort rna sequencing reveals changes in the micrornaome of transdifferentiating hepatic stellate cells that are conserved between human and rat
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/8f906b3b042a46b4911aff0dbd9c06a0
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