Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease leading to degeneration of motor neurons (MNs). Epigenetic modification of gene expression is increasingly recognized as potential disease mechanism. In the present study we generated motor neurons from induced pluripotent stem cel...

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Autores principales:	T. Hartung, M. Rhein, N. Kalmbach, N. Thau-Habermann, M. Naujock, L. Müschen, H. Frieling, J. Sterneckert, A. Hermann, F. Wegner, S. Petri
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	amyotrophic lateral sclerosis induced pluripotent stem cells derived motor neurons FUS methylation DNA methyltransferases Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/489ab3ddbc6b46108b876a20cbaa97fb
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spelling	oai:doaj.org-article:489ab3ddbc6b46108b876a20cbaa97fb2021-11-19T07:39:13ZMethylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients2296-634X10.3389/fcell.2021.774751https://doaj.org/article/489ab3ddbc6b46108b876a20cbaa97fb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.774751/fullhttps://doaj.org/toc/2296-634XAmyotrophic lateral sclerosis (ALS) is a rapidly progressive disease leading to degeneration of motor neurons (MNs). Epigenetic modification of gene expression is increasingly recognized as potential disease mechanism. In the present study we generated motor neurons from induced pluripotent stem cells from ALS patients carrying a mutation in the fused in sarcoma gene (FUS) and analyzed expression and promoter methylation of the FUS gene and expression of DNA methyltransferases (DNMTs) compared to healthy control cell lines. While mutant FUS neural progenitor cells (NPCs) did not show a difference in FUS and DNMT expression compared to healthy controls, differentiated mutant FUS motor neurons showed significantly lower FUS expression, higher DNMT expression and higher methylation of the proximal FUS gene promoter. Immunofluorescence revealed perceived proximity of cytoplasmic FUS aggregates in ALS MNs together with 5-methylcytosin (5-mC). Targeting disturbed methylation in ALS may therefore restore transcriptional alterations and represent a novel therapeutic strategy.T. HartungT. HartungM. RheinN. KalmbachN. Thau-HabermannM. NaujockM. NaujockL. MüschenH. FrielingJ. SterneckertA. HermannA. HermannF. WegnerS. PetriFrontiers Media S.A.articleamyotrophic lateral sclerosisinduced pluripotent stem cells derived motor neuronsFUSmethylationDNA methyltransferasesBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amyotrophic lateral sclerosis induced pluripotent stem cells derived motor neurons FUS methylation DNA methyltransferases Biology (General) QH301-705.5
spellingShingle	amyotrophic lateral sclerosis induced pluripotent stem cells derived motor neurons FUS methylation DNA methyltransferases Biology (General) QH301-705.5 T. Hartung T. Hartung M. Rhein N. Kalmbach N. Thau-Habermann M. Naujock M. Naujock L. Müschen H. Frieling J. Sterneckert A. Hermann A. Hermann F. Wegner S. Petri Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients
description	Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease leading to degeneration of motor neurons (MNs). Epigenetic modification of gene expression is increasingly recognized as potential disease mechanism. In the present study we generated motor neurons from induced pluripotent stem cells from ALS patients carrying a mutation in the fused in sarcoma gene (FUS) and analyzed expression and promoter methylation of the FUS gene and expression of DNA methyltransferases (DNMTs) compared to healthy control cell lines. While mutant FUS neural progenitor cells (NPCs) did not show a difference in FUS and DNMT expression compared to healthy controls, differentiated mutant FUS motor neurons showed significantly lower FUS expression, higher DNMT expression and higher methylation of the proximal FUS gene promoter. Immunofluorescence revealed perceived proximity of cytoplasmic FUS aggregates in ALS MNs together with 5-methylcytosin (5-mC). Targeting disturbed methylation in ALS may therefore restore transcriptional alterations and represent a novel therapeutic strategy.
format	article
author	T. Hartung T. Hartung M. Rhein N. Kalmbach N. Thau-Habermann M. Naujock M. Naujock L. Müschen H. Frieling J. Sterneckert A. Hermann A. Hermann F. Wegner S. Petri
author_facet	T. Hartung T. Hartung M. Rhein N. Kalmbach N. Thau-Habermann M. Naujock M. Naujock L. Müschen H. Frieling J. Sterneckert A. Hermann A. Hermann F. Wegner S. Petri
author_sort	T. Hartung
title	Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients
title_short	Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients
title_full	Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients
title_fullStr	Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients
title_full_unstemmed	Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients
title_sort	methylation and expression of mutant fus in motor neurons differentiated from induced pluripotent stem cells from als patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/489ab3ddbc6b46108b876a20cbaa97fb
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Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients

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