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干细胞极性的形成机制如何塑造人类大脑皮层。

How mechanisms of stem cell polarity shape the human cerebral cortex.

机构信息

Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.

The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.

出版信息

Nat Rev Neurosci. 2022 Dec;23(12):711-724. doi: 10.1038/s41583-022-00631-3. Epub 2022 Sep 30.

Abstract

Apical-basal progenitor cell polarity establishes key features of the radial and laminar architecture of the developing human cortex. The unique diversity of cortical stem cell populations and an expansion of progenitor population size in the human cortex have been mirrored by an increase in the complexity of cellular processes that regulate stem cell morphology and behaviour, including their polarity. The study of human cells in primary tissue samples and human stem cell-derived model systems (such as cortical organoids) has provided insight into these processes, revealing that protein complexes regulate progenitor polarity by controlling cell membrane adherence within appropriate cortical niches and are themselves regulated by cytoskeletal proteins, signalling molecules and receptors, and cellular organelles. Studies exploring how cortical stem cell polarity is established and maintained are key for understanding the features of human brain development and have implications for neurological dysfunction.

摘要

顶端-基底祖细胞极性确定了人类皮质发育的放射状和层状结构的关键特征。人类皮质中皮层干细胞群体的独特多样性和祖细胞群体大小的扩大,反映了调节干细胞形态和行为的细胞过程的复杂性增加,包括其极性。对原代组织样本中的人类细胞和人类干细胞衍生的模型系统(如皮质类器官)的研究提供了对这些过程的深入了解,揭示了蛋白质复合物通过控制适当皮质龛位中的细胞膜附着来调节祖细胞极性,并且自身受到细胞骨架蛋白、信号分子和受体以及细胞细胞器的调节。探索皮质干细胞极性如何建立和维持的研究对于理解人类大脑发育的特征至关重要,并对神经功能障碍具有重要意义。

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