Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis.
Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis.
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DOI：
10.1038/s41467-018-05099-3
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发表时间：
2018-08-21
影响因子：
16.6
通讯作者：
Petritsch CK
中科院分区：
文献类型：
--
作者：
Daynac M;Chouchane M;Collins HY;Murphy NE;Andor N;Niu J;Fancy SPJ;Stallcup WB;Petritsch CK
少突胶质细胞祖细胞（OPC）经历不对称细胞分裂（ACD）以产生一个OPC和一个分化的少突胶质细胞（OL）后代。OL后代中促有丝分裂蛋白聚糖和OPC标记物NG 2的丢失是指示分化定型的未知机制的最早免疫表型变化。在这里，我们报告说，表达的果蝇肿瘤抑制因子致死巨幼虫1（LGL 1）的小鼠同源物诱导OL分化。Lgl 1条件性敲除OPC后代保留NG 2并显示出降低的OL分化，同时以不对称分裂为代价进行更对称的自我更新分裂。此外，OPC中的Lgll和半合子Ink 4a/Arf敲除协同诱导胶质瘤形成。时间推移和全内反射显微镜揭示了一个关键的作用，在NG 2内吞路由和链接异常NG 2回收失败的分化Lgl 1。这些数据确立了Lgl 1作为健康和脱髓鞘小鼠脑中胶质瘤发生的抑制剂和不对称分裂和分化的正调节剂。少突胶质细胞祖细胞（OPCs）经历不对称细胞分裂，并且这种机制的破坏可以产生少突胶质细胞瘤前体。在这里，Daynac及其同事表明，Lgl 1通过干扰内吞途径调节OPCs的不对称分裂和分化，并且Lgl 1敲除可导致胶质瘤发生。
Oligodendrocyte progenitor cells (OPC) undergo asymmetric cell division (ACD) to generate one OPC and one differentiating oligodendrocyte (OL) progeny. Loss of pro-mitotic proteoglycan and OPC marker NG2 in the OL progeny is the earliest immunophenotypic change of unknown mechanism that indicates differentiation commitment. Here, we report that expression of the mouse homolog of Drosophila tumor suppressor Lethal giant larvae 1 (Lgl1) is induced during OL differentiation. Lgl1 conditional knockout OPC progeny retain NG2 and show reduced OL differentiation, while undergoing more symmetric self-renewing divisions at the expense of asymmetric divisions. Moreover, Lgl1 and hemizygous Ink4a/Arf knockouts in OPC synergistically induce gliomagenesis. Time lapse and total internal reflection microscopy reveals a critical role for Lgl1 in NG2 endocytic routing and links aberrant NG2 recycling to failed differentiation. These data establish Lgl1 as a suppressor of gliomagenesis and positive regulator of asymmetric division and differentiation in the healthy and demyelinated murine brain. Oligodendrocyte progenitor cells (OPCs) undergo asymmetric cell division, and disruption of such mechanism can generate oligodendroglioma precursors. Here, Daynac and colleagues show that Lgl1 regulates asymmetric division and differentiation of OPCs by interfering with the endocytosis pathway, and that Lgl1 knockout can lead to gliomagenesis.
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影响因子：
25
作者：
Hill, Robert A.;Patel, Kiran D.;Goncalves, Christopher M.;Grutzendler, Jaime;Nishiyama, Akiko
通讯作者：
Nishiyama, Akiko
影响因子：
5.6
作者：
He L;Lu QR
通讯作者：
Lu QR
DOI：
10.1111/tra.12152
发表时间：
2014-04
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Chandrasekar I;Goeckeler ZM;Turney SG;Wang P;Wysolmerski RB;Adelstein RS;Bridgman PC
通讯作者：
Bridgman PC
影响因子：
4.8
作者：
Goretzki, L;Burg, MA;Stallcup, WB
通讯作者：
Stallcup, WB
影响因子：
--
作者：
Grossauer, Stefan;Koeck, Katharina;Petritsch, Claudia K.
通讯作者：
Petritsch, Claudia K.