Neural stem cell differentiation is dictated by distinct actions of nuclear receptor corepressors and histone deacetylases.
Neural stem cell differentiation is dictated by distinct actions of nuclear receptor corepressors and histone deacetylases.
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DOI：
10.1016/j.stemcr.2014.07.008
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发表时间：
2014-09-09
影响因子：
5.9
通讯作者：
Hermanson, Ola
中科院分区：
文献类型：
--
作者：
Castelo-Branco, Goncalo G;Lilja, Tobias;Wallenborg, Karolina;Falcao, Ana M.;Marques, Sueli C.;Gracias, Aileen;Solum, Derek;Paap, Ricardo;Walfridsson, Julian;Teixeira, Ana I.;Rosenfeld, Michael G.;Jepsen, Kristen;Hermanson, Ola
包括视黄酸（RA）和甲状腺激素（T3）的信号因子促进皮质神经干细胞（NSCs）向神经元、少突胶质细胞和星形胶质细胞分化。然而，控制这些分化程序的转录抑制因子检查点的功能特异性仍然不清楚。在这里，我们通过全基因组分析表明，组蛋白去乙酰化酶（HDAC）2和HDAC 3在神经干细胞中的神经元和少突胶质细胞相关基因上显示重叠和不同的启动子占用。HDAC 3而非HDAC 2的缺乏启动了NSC中的神经元分化途径。辅阻遏物NCOR或HDAC 2的消融，结合T3治疗，导致少突胶质细胞基因的表达增加，揭示了直接HDAC 2介导的Sox 8和Sox 10表达的抑制。有趣的是，Sox 10也需要通过抑制干细胞编程因子如Sox 2和Sox 9来维持更分化的状态。因此，NCOR和HDAC的独特和非冗余作用对于控制神经祖细胞的谱系进展和分化程序至关重要。ChIP-seq揭示了HDAC 2和HDAC 3在NCOR的缺失促进NSC的少突胶质细胞分化HDAC 2通过SOX 2占据的增强子控制OL分化中的Sox 10表达Sox 10是维持晚期OL前体中的分化状态所必需的ChIP-seq揭示了HDAC 2和HDAC 3在神经元和少突胶质细胞中显示重叠和不同的启动子占据。相关基因HDAC 3敲低启动神经元分化。Hermanson，Castelo-Branco及其同事表明，Ncor或在T3存在下Hdac 2的消融导致少突胶质细胞基因表达增加，揭示了HDAC 2介导的Sox 10表达抑制。Sox 10是通过抑制包括Sox 2和Sox 9在内的干细胞因子来维持更分化状态所必需的。
Signaling factors including retinoic acid (RA) and thyroid hormone (T3) promote neuronal, oligodendrocyte, and astrocyte differentiation of cortical neural stem cells (NSCs). However, the functional specificity of transcriptional repressor checkpoints controlling these differentiation programs remains unclear. Here, we show by genome-wide analysis that histone deacetylase (HDAC)2 and HDAC3 show overlapping and distinct promoter occupancy at neuronal and oligodendrocyte-related genes in NSCs. The absence of HDAC3, but not HDAC2, initiated a neuronal differentiation pathway in NSCs. The ablation of the corepressor NCOR or HDAC2, in conjunction with T3 treatment, resulted in increased expression of oligodendrocyte genes, revealing a direct HDAC2-mediated repression of Sox8 and Sox10 expression. Interestingly, Sox10 was required also for maintaining the more differentiated state by repression of stem cell programming factors such as Sox2 and Sox9. Distinct and nonredundant actions of NCORs and HDACs are thus critical for control of lineage progression and differentiation programs in neural progenitors. ChIP-seq reveals distinct and overlapping occupancy of HDAC2 and HDAC3 in NSCs Absence of NCOR promotes oligodendrocyte differentiation of NSCs HDAC2 controls Sox10 expression in OL differentiation via a SOX2-occupied enhancer Sox10 is required for maintaining the differentiated state in late OL precursors ChIP-seq in neural stem cells revealed that HDAC2 and HDAC3 show overlapping and distinct promoter occupancy at neuronal and oligodendrocyte-related genes. HDAC3 knockdown initiated neuronal differentiation. Hermanson, Castelo-Branco, and colleagues show that ablation of Ncor or, in the presence of T3, Hdac2 resulted in increased expression of oligodendrocyte genes, unveiling an HDAC2-mediated repression of Sox10 expression. Sox10 was required for maintaining a more differentiated state by repression of stem cell factors including Sox2 and Sox9.
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DOI：
10.1242/dev.098418
发表时间：
2014-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hoffmann SA;Hos D;Küspert M;Lang RA;Lovell-Badge R;Wegner M;Reiprich S
通讯作者：
Reiprich S
影响因子：
64.8
作者：
Jepsen, Kristen;Solum, Derek;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
影响因子：
4.6
作者：
Covey, Matthew V.;Streb, Jeffrey W.;Ballas, Nurit
通讯作者：
Ballas, Nurit
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
64.5
作者：
Jepsen, K;Hermanson, O;Rosenfeld, MG
通讯作者：
Rosenfeld, MG