Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration.

Brügger, Valérie; Duman, Mert; Bochud, Maëlle; Münger, Emmanuelle; Heller, Manfred; Ruff, Sophie; Jacob, Claire (2017). Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration. Nature communications, 8(14272), p. 14272. Nature Publishing Group 10.1038/ncomms14272

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The peripheral nervous system (PNS) regenerates after injury. However, regeneration is often compromised in the case of large lesions, and the speed of axon reconnection to their target is critical for successful functional recovery. After injury, mature Schwann cells (SCs) convert into repair cells that foster axonal regrowth, and redifferentiate to rebuild myelin. These processes require the regulation of several transcription factors, but the driving mechanisms remain partially understood. Here we identify an early response to nerve injury controlled by histone deacetylase 2 (HDAC2), which coordinates the action of other chromatin-remodelling enzymes to induce the upregulation of Oct6, a key transcription factor for SC development. Inactivating this mechanism using mouse genetics allows earlier conversion into repair cells and leads to faster axonal regrowth, but impairs remyelination. Consistently, short-term HDAC1/2 inhibitor treatment early after lesion accelerates functional recovery and enhances regeneration, thereby identifying a new therapeutic strategy to improve PNS regeneration after lesion.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Massenspektrometrie- und Proteomics-Labor
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Protein- und Zellbiologie

UniBE Contributor:

Heller, Manfred

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

02 Feb 2018 12:07

Last Modified:

06 Feb 2018 10:27

Publisher DOI:

10.1038/ncomms14272

PubMed ID:

28139683

BORIS DOI:

10.7892/boris.109708

URI:

https://boris.unibe.ch/id/eprint/109708

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