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HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State

Rosenberg, LH; Cattin, A-L; Fontana, X; Harford-Wright, E; Burden, JJ; White, IJ; Smith, JG; ... Lloyd, AC; + view all (2018) HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State. Cell Reports , 25 (10) pp. 2755-2765. 10.1016/j.celrep.2018.11.045. Green open access

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Abstract

The formation of myelinating Schwann cells (mSCs) involves the remarkable biogenic process, which rapidly generates the myelin sheath. Once formed, the mSC transitions to a stable homeostatic state, with loss of this stability associated with neuropathies. The histone deacetylases histone deacetylase 1 (HDAC1) and HDAC2 are required for the myelination transcriptional program. Here, we show a distinct role for HDAC3, in that, while dispensable for the formation of mSCs, it is essential for the stability of the myelin sheath once formed-with loss resulting in progressive severe neuropathy in adulthood. This is associated with the prior failure to downregulate the biogenic program upon entering the homeostatic state leading to hypertrophy and hypermyelination of the mSCs, progressing to the development of severe myelination defects. Our results highlight distinct roles of HDAC1/2 and HDAC3 in controlling the differentiation and homeostatic states of a cell with broad implications for the understanding of this important cell-state transition.

Type: Article
Title: HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2018.11.045
Publisher version: http://doi.org/10.1016/j.celrep.2018.11.045
Language: English
Additional information: Copyright © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Keywords: HDACs, Schwann cells, biogenesis, homeostasis, neuropathy, peripheral nerve
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10064019
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