Cell environment shapes TDP-43 function with implications in neuronal and muscle disease

NYGC ALS Consortium

Research output: Contribution to journalArticlepeer-review


TDP-43 (TAR DNA-binding protein 43) aggregation and redistribution are recognised as a hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. As TDP-43 inclusions have recently been described in the muscle of inclusion body myositis patients, this highlights the need to understand the role of TDP-43 beyond the central nervous system. Using RNA-seq, we directly compare TDP-43-mediated RNA processing in muscle (C2C12) and neuronal (NSC34) mouse cells. TDP-43 displays a cell-type-characteristic behaviour targeting unique transcripts in each cell-type, which is due to characteristic expression of RNA-binding proteins, that influence TDP-43’s performance and define cell-type specific splicing. Among splicing events commonly dysregulated in both cell lines, we identify some that are TDP-43-dependent also in human cells. Inclusion levels of these alternative exons are altered in tissues of patients suffering from FTLD and IBM. We therefore propose that TDP-43 dysfunction contributes to disease development either in a common or a tissue-specific manner.

Original languageEnglish
Article number314
JournalCommunications Biology
Issue number1
StatePublished - Dec 2022


FundersFunder number
European Reference Network for Neuromuscular Diseases
Fondazione IRCCS Ca’ Granda
Fondazione Malattie Miotoniche
Neurodegenerative Disease
Ospedale Maggiore Policlinico
ALS Association15-LGCA-234
ALS Association
King’s College London
Tow Foundation
Medical Research CouncilMR/T001712/1
Medical Research Council
Fondazione Cariplo
Ministero della Salute
Agenzia di Ricerca per la Sclerosi Laterale Amiotrofica
Fondazione per la Ricerca Biomedica


    Dive into the research topics of 'Cell environment shapes TDP-43 function with implications in neuronal and muscle disease'. Together they form a unique fingerprint.

    Cite this