Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies

Abstract Objective To define the transcriptomic changes responsible for the histologic alterations in skeletal muscle and their progression in collagen VI‐related muscular dystrophy (COL6‐RD). Methods COL6‐RD patient muscle biopsies were stratified into three groups based on the overall level of pat...

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Autores principales:	Eleonora Guadagnin, Payam Mohassel, Kory R. Johnson, Lin Yang, Mariarita Santi, Prech Uapinyoying, Jahannaz Dastgir, Ying Hu, Allissa Dillmann, Mark R. Cookson, A. Reghan Foley, Carsten G. Bönnemann
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/dda1fa8944874dd69ded9e0f376f266a
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spelling	oai:doaj.org-article:dda1fa8944874dd69ded9e0f376f266a2021-11-22T11:11:52ZTranscriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies2328-950310.1002/acn3.51450https://doaj.org/article/dda1fa8944874dd69ded9e0f376f266a2021-11-01T00:00:00Zhttps://doi.org/10.1002/acn3.51450https://doaj.org/toc/2328-9503Abstract Objective To define the transcriptomic changes responsible for the histologic alterations in skeletal muscle and their progression in collagen VI‐related muscular dystrophy (COL6‐RD). Methods COL6‐RD patient muscle biopsies were stratified into three groups based on the overall level of pathologic severity considering degrees of fibrosis, muscle fiber atrophy, and fatty replacement of muscle tissue. Using microarray and RNA‐Seq, we then performed global gene expression profiling on the same muscle biopsies and compared their transcriptome with age‐ and sex‐matched controls. Results COL6‐RD muscle biopsy transcriptomes as a group revealed prominent upregulation of muscle extracellular matrix component genes and the downregulation of skeletal muscle and mitochondrion‐specific genes. Upregulation of the TGFβ pathway was the most conspicuous change across all biopsies and was fully evident even in the mildest/earliest histological group. There was no difference in the overall transcriptional signature between the different histologic groups but polyserial analysis identified relative changes along with COL6‐RD histological severity. Interpretation Overall, our study establishes the prominent dysregulation of extracellular matrix genes, TGFβ signaling, and its downstream cellular pathways at the transcriptomic level in COL6‐RD muscle.Eleonora GuadagninPayam MohasselKory R. JohnsonLin YangMariarita SantiPrech UapinyoyingJahannaz DastgirYing HuAllissa DillmannMark R. CooksonA. Reghan FoleyCarsten G. BönnemannWileyarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENAnnals of Clinical and Translational Neurology, Vol 8, Iss 11, Pp 2184-2198 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Eleonora Guadagnin Payam Mohassel Kory R. Johnson Lin Yang Mariarita Santi Prech Uapinyoying Jahannaz Dastgir Ying Hu Allissa Dillmann Mark R. Cookson A. Reghan Foley Carsten G. Bönnemann Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies
description	Abstract Objective To define the transcriptomic changes responsible for the histologic alterations in skeletal muscle and their progression in collagen VI‐related muscular dystrophy (COL6‐RD). Methods COL6‐RD patient muscle biopsies were stratified into three groups based on the overall level of pathologic severity considering degrees of fibrosis, muscle fiber atrophy, and fatty replacement of muscle tissue. Using microarray and RNA‐Seq, we then performed global gene expression profiling on the same muscle biopsies and compared their transcriptome with age‐ and sex‐matched controls. Results COL6‐RD muscle biopsy transcriptomes as a group revealed prominent upregulation of muscle extracellular matrix component genes and the downregulation of skeletal muscle and mitochondrion‐specific genes. Upregulation of the TGFβ pathway was the most conspicuous change across all biopsies and was fully evident even in the mildest/earliest histological group. There was no difference in the overall transcriptional signature between the different histologic groups but polyserial analysis identified relative changes along with COL6‐RD histological severity. Interpretation Overall, our study establishes the prominent dysregulation of extracellular matrix genes, TGFβ signaling, and its downstream cellular pathways at the transcriptomic level in COL6‐RD muscle.
format	article
author	Eleonora Guadagnin Payam Mohassel Kory R. Johnson Lin Yang Mariarita Santi Prech Uapinyoying Jahannaz Dastgir Ying Hu Allissa Dillmann Mark R. Cookson A. Reghan Foley Carsten G. Bönnemann
author_facet	Eleonora Guadagnin Payam Mohassel Kory R. Johnson Lin Yang Mariarita Santi Prech Uapinyoying Jahannaz Dastgir Ying Hu Allissa Dillmann Mark R. Cookson A. Reghan Foley Carsten G. Bönnemann
author_sort	Eleonora Guadagnin
title	Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies
title_short	Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies
title_full	Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies
title_fullStr	Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies
title_full_unstemmed	Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies
title_sort	transcriptome analysis of collagen vi‐related muscular dystrophy muscle biopsies
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/dda1fa8944874dd69ded9e0f376f266a
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Transcriptome analysis of collagen VI‐related muscular dystrophy muscle biopsies

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