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在哺乳动物神经干细胞分裂过程中,双链RNA结合蛋白Staufen2的不对称分离促进了谱系的发展
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2022.06.11 贵州

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Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression.
在哺乳动物神经干细胞分裂过程中,双链RNA结合蛋白Staufen2的不对称分离促进了谱系的发展
|核心内容:
细胞分裂不对称是神经发育的基本特征,调节不当可能导致脑部异常或肿瘤形成。
Stau2 Expression in Embryonic Mouse Cortex
在细胞不对称分裂过程中,分子决定因子优先分离到一个子细胞中,以确定其命运。
一个重要的目标是确定神经前体细胞中的不对称决定因素,这些决定因素可能是肿瘤抑制因子,也可能是特定神经命运的诱导者。
在这里,我们证明了双链RNA结合蛋白Stau2在发育中的小鼠皮层的祖细胞分裂过程中是不对称分布的,优先分离到Tbr2(+)神经母细胞子代,带走了RNA的一个子集。
Stau2基因敲除刺激分化,过度表达产生脑室周围神经元团,证明其对正常皮质发育的功能重要性。
Stau2 Knockdown Promotes Differentiation In Vitro
(A) Stau2 knockdown in E10–11 cortical cultures fixed after 3 days in culture.Clones show fewer Pax6+ cells (cyan) after shRNA Stau2 knockdowncompared with control, quantified in (C).
(B) Clones show more Tbr2+ cells (red) after shRNA Stau2 compared withcontrol, quantified in (D).(E) Quantification of b-tubulin III staining reveals more neurons after shRNAStau2 knockdown.
我们免疫沉淀Stau2以检测其货运mRNA,发现富集了已知的不对称和基底细胞决定簇,如Trim32,并确定了候选基因,包括参与初级纤毛功能的一个子集。
原文摘要:
Asymmetric cell divisions are a fundamental feature of neural development, and misregulation can lead to brain abnormalities or tumor formation.
During an asymmetric cell division, molecular determinants are segregated preferentially into one daughter cell to specify its fate.
An important goal is to identify the asymmetric determinants in neural progenitor cells, which could be tumor suppressors or inducers of specific neural fates.
Here, we show that the double-stranded RNA-binding protein Stau2 is distributed asymmetrically during progenitor divisions in the developing mouse cortex, preferentially segregating into the Tbr2(+) neuroblast daughter, taking with it a subset of RNAs.
Knockdown of Stau2 stimulates differentiation and overexpression produces periventricular neuronal masses, demonstrating its functional importance for normal cortical development.
We immunoprecipitated Stau2 to examine its cargo mRNAs, and found enrichment for known asymmetric and basal cell determinants, such as Trim32, and identified candidates, including a subset involved in primary cilium function.
参考文献:
Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression.
https://sci-hub.ren/10.1016/j.stem.2012.06.010
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