HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State.
HDAC3 Regulates the Transition to the Homeostatic Myelinating Schwann Cell State.
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HDAC3 调节向稳态髓鞘雪旺细胞状态的转变。
DOI：
10.1016/j.celrep.2018.11.045
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发表时间：
2018
期刊：
影响因子：
8.8
通讯作者：
Rosenberg LH
中科院分区：
文献类型：
--
作者：
Rosenberg LH
髓鞘化雪旺细胞（mSCs）的形成涉及一个显著的生物生成过程，该过程迅速生成髓鞘。一旦形成，间充质干细胞转变为稳定的体内平衡状态，这种稳定性的丧失与神经病变有关。组蛋白去乙酰化酶组蛋白去乙酰化酶1 （HDAC1）和HDAC2是髓鞘形成转录程序所必需的。在这里，我们展示了HDAC3的独特作用，尽管它对于mSCs的形成是必不可少的，但它对于髓鞘形成后的稳定性是必不可少的——髓鞘的缺失会导致成年期进行性严重神经病变。这与在进入稳态状态时未能下调生物源性程序导致间充质干细胞肥大和髓鞘增生，进而发展为严重髓鞘形成缺陷有关。我们的研究结果强调了HDAC1/2和HDAC3在控制细胞分化和稳态中的不同作用，这对理解这种重要的细胞状态转变具有广泛的意义。
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.