Proteomics

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Mouse sciatic nerve LC-MSMS - Delaying histone deacetylase response to injury accelerates conversion into repair Schwann cells and nerve regeneration


ABSTRACT: The peripheral nervous system (PNS) regenerates after injury. However regeneration is often compromised in case of large lesions, the speed of axon reconnection to their target being 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 injury controlled by histone deacetylase (HDAC)2, which coordinates the action of other chromatin-remodeling enzymes to induce the upregulation of Oct6, a key transcription factor for Schwann cell 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Nerve Cord

SUBMITTER: Manfred Heller  

LAB HEAD: Claire Jacob

PROVIDER: PXD005383 | Pride | 2018-10-17

REPOSITORIES: Pride

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Publications

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

Brügger Valérie V   Duman Mert M   Bochud Maëlle M   Münger Emmanuelle E   Heller Manfred M   Ruff Sophie S   Jacob Claire C  

Nature communications 20170131


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. He  ...[more]

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