Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells.
Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells.
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DOI：
10.7554/elife.67074
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发表时间：
2021-11-29
期刊：
影响因子：
7.7
通讯作者：
Hatten ME
中科院分区：
文献类型：
--
作者：
Behesti H;Kocabas A;Buchholz DE;Carroll TS;Hatten ME
大脑发育受到跨物种保守转录程序的调节，但人们对产生物种特异性特征的不同机制知之甚少。在大脑区域中，与非人类灵长类动物和啮齿动物相比，人类小脑组织发生的复杂性有所不同，因此开发生成与正在发育的人类小脑中的神经元非常相似的人类小脑神经元的方法非常重要。我们报告了一种从人类多能干细胞 (hPSC) 中衍生出人类 ATOH1 谱系（兴奋性小脑神经元的前体）的快速方案。移植到幼年小鼠体内后，hPSC 衍生的小脑颗粒细胞沿着神经胶质纤维迁移并整合到小脑皮质中。通过翻译核糖体亲和纯化序列，我们发现了人类外颗粒层中 RBFOX3 (NeuN) 和 NEUROD1 表达的意外时间变化，这通常与分化的神经元相关。与小鼠相比，这种分子差异可能使人类小脑的发育得以延长。
Brain development is regulated by conserved transcriptional programs across species, but little is known about the divergent mechanisms that create species-specific characteristics. Among brain regions, human cerebellar histogenesis differs in complexity compared with nonhuman primates and rodents, making it important to develop methods to generate human cerebellar neurons that closely resemble those in the developing human cerebellum. We report a rapid protocol for the derivation of the human ATOH1 lineage, the precursor of excitatory cerebellar neurons, from human pluripotent stem cells (hPSCs). Upon transplantation into juvenile mice, hPSC-derived cerebellar granule cells migrated along glial fibers and integrated into the cerebellar cortex. By Translational Ribosome Affinity Purification-seq, we identified an unexpected temporal shift in the expression of RBFOX3 (NeuN) and NEUROD1, which are classically associated with differentiated neurons, in the human outer external granule layer. This molecular divergence may enable the protracted development of the human cerebellum compared to mice.
影响因子：
2.7
作者：
Guo, Qiuxia;Li, Kairong;Sunmonu, N. Abimbola;Li, James Y. H.
通讯作者：
Li, James Y. H.