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Publication : HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State.

First Author  Rosenberg LH Year  2018
Journal  Cell Rep Volume  25
Issue  10 Pages  2755-2765.e5
PubMed ID  30517863 Mgi Jnum  J:271183
Mgi Id  MGI:6278449 Doi  10.1016/j.celrep.2018.11.045
Citation  Rosenberg LH, et al. (2018) HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State. Cell Rep 25(10):2755-2765.e5
abstractText  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.
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