The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development
The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development
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CTNNBIP1-CLSTN1融合转录本调节人类新皮质发育
DOI：
10.1016/j.celrep.2021.109290
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发表时间：
2021-06-29
期刊：
影响因子：
8.8
通讯作者：
Luo, Zhen-Ge
中科院分区：
文献类型：
--
作者：
Ou, Min-Yi;Xiao, Qi;Luo, Zhen-Ge
融合转录物或RNA已在紊乱和健康的人类组织和细胞中发现;然而，它们在脑发育中的生理功能仍然未知。在分析沉积的RNA序列库，涵盖早期到中期胚胎阶段，我们确定了1,055融合转录本存在于发展中的新皮层。有趣的是，98个融合转录本在各种神经祖细胞（NP）或神经元中表现出不同的表达模式。我们专注于CTNNBIP 1-CLSTN 1（CTCL），它富含外放射状胶质细胞，有助于人类进化过程中的皮质扩张。有趣的是，CTCL在培养的人脑类器官中的下调导致NP和早熟神经元分化的显著减少，导致类器官生长受损。此外，CTCL的表达微调Wnt/β-连环蛋白信号，控制皮质图案。总之，这项工作提供了证据表明融合转录本在人类大脑发育和进化中的重要作用。
Fusion transcripts or RNAs have been found in both disordered and healthy human tissues and cells; however, their physiological functions in the brain development remain unknown. In the analysis of deposited RNA-sequence libraries covering early to middle embryonic stages, we identify 1,055 fusion transcripts present in the developing neocortex. Interestingly, 98 fusion transcripts exhibit distinct expression patterns in various neural progenitors (NPs) or neurons. We focus on CTNNBIP1-CLSTN1 (CTCL), which is enriched in outer radial glial cells that contribute to cortex expansion during human evolution. Intriguingly, downregulation of CTCL in cultured human cerebral organoids causes marked reduction in NPs and precocious neuronal differentiation, leading to impairment of organoid growth. Furthermore, the expression of CTCL fine-tunes Wnt/beta-catenin signaling that controls cortex patterning. Together, this work provides evidence indicating important roles of fusion transcript in human brain development and evolution.