PRC2 Acts as a Critical Timer That Drives Oligodendrocyte Fate over Astrocyte Identity by Repressing the Notch Pathway.
PRC2 Acts as a Critical Timer That Drives Oligodendrocyte Fate over Astrocyte Identity by Repressing the Notch Pathway.
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DOI：
10.1016/j.celrep.2020.108147
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发表时间：
2020-09-15
期刊：
影响因子：
8.8
通讯作者：
Lee SK
中科院分区：
文献类型：
--
作者：
Wang W;Cho H;Kim D;Park Y;Moon JH;Lim SJ;Yoon SM;McCane M;Aicher SA;Kim S;Emery B;Lee JW;Lee S;Park Y;Lee SK
PRC2 creates the repressive mark histone H3 Lys27 trimethylation. Although PRC2 is involved in various biological processes, its role in glial development remains ambiguous. Here, we show that PRC2 is required for oligodendrocyte (OL) differentiation and myelination, but not for OL precursor formation. PRC2-deficient OL lineage cells differentiate into OL precursors, but they fail to trigger the molecular program for myelination, highlighting that PRC2 is essential for directing the differentiation timing of OL precursors. PRC2 null OL lineage cells aberrantly induce Notch pathway genes and acquire astrocytic features. The repression of the Notch pathway restores the myelination program and inhibits abnormal astrocytic differentiation in the PRC2-deficient OL lineage, indicating that Notch is a major target of PRC2. Altogether, our studies propose a specific action of PRC2 as a novel gatekeeper that determines the glial fate choice and the timing of OL lineage progression and myelination by impinging on the Notch pathway. Wang et al. show that the polycomb repressive complex PRC2 is required for the differentiation of oligodendrocyte precursors to myelinating oligodendrocytes. They further show that PRC2 promotes oligodendrocyte differentiation and inhibits erroneous astrocytic fate by repressing the Notch pathway.
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影响因子：
25
作者：
Glasgow, Stacey M.;Zhu, Wenyi;Stolt, C. Claus;Huang, Teng-Wei;Chen, Fuyi;LoTurco, Joseph J.;Neul, Jeffrey L.;Wegner, Michael;Mohila, Carrie;Deneen, Benjamin
通讯作者：
Deneen, Benjamin
影响因子：
5.6
作者：
He L;Lu QR
通讯作者：
Lu QR
NOTCH1控制脊髓中的少突胶质细胞分化。
影响因子：
7.8
作者：
Genoud, Stephane;Lappe-Siefke, Corinna;Goebbels, Sandra;Radtke, Freddy;Aguet, Michel;Scherer, Steven S;Suter, Ueli;Nave, Klaus-Armin;Mantei, Ned
通讯作者：
Mantei, Ned
影响因子：
8.8
作者：
Clovis YM;Seo SY;Kwon JS;Rhee JC;Yeo S;Lee JW;Lee S;Lee SK
通讯作者：
Lee SK
影响因子：
2.8
作者：
Aicher SA;Hermes SM;Whittier KL;Hegarty DM
通讯作者：
Hegarty DM