Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead
Trithorax maintains the functional heterogeneity of neural stem cells through the transcription factor Buttonhead
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DOI：
10.7554/elife.03502
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发表时间：
2014-10-06
期刊：
影响因子：
7.7
通讯作者：
Lee, Cheng-Yu
中科院分区：
文献类型：
--
作者：
Komori, Hideyuki;Xiao, Qi;Lee, Cheng-Yu
维持干细胞功能异质性的机制尚不清楚，干细胞产生器官发生所需的多种分化细胞类型。在这里，我们报告 Trithorax (Trx) 积极维持发育中的果蝇幼虫大脑中神经干细胞（神经母细胞）的异质性。 trx突变的II型神经母细胞逐渐采用I型神经母细胞的功能特性，失去产生中间神经祖细胞（INP）并直接产生分化细胞的能力。 Trx 部分通过 SET1/MLL 复合物的组蛋白甲基转移酶活性维持按钮头 (btd) 基因座中的染色质处于活跃状态来调节 II 型神经母细胞功能特性。一致地，btd 对于引发 II 型神经母细胞功能身份是必要且充分的。此外，btd 的过度表达恢复了 trx 突变型 II 型神经母细胞中产生 INP 的能力。因此，Trx 通过表观遗传促进 Btd 表达来指示 II 型神经母细胞功能同一性，从而维持神经母细胞功能异质性。
The mechanisms that maintain the functional heterogeneity of stem cells, which generates diverse differentiated cell types required for organogenesis, are not understood. Here, we report that Trithorax (Trx) actively maintains the heterogeneity of neural stem cells (neuroblasts) in the developing Drosophila larval brain. trx mutant type II neuroblasts gradually adopt a type I neuroblast functional identity, losing the competence to generate intermediate neural progenitors (INPs) and directly generating differentiated cells. Trx regulates a type II neuroblast functional identity in part by maintaining chromatin in the buttonhead (btd) locus in an active state through the histone methyltransferase activity of the SET1/MLL complex. Consistently, btd is necessary and sufficient for eliciting a type II neuroblast functional identity. Furthermore, over-expression of btd restores the competence to generate INPs in trx mutant type II neuroblasts. Thus, Trx instructs a type II neuroblast functional identity by epigenetically promoting Btd expression, thereby maintaining neuroblast functional heterogeneity.