Verheijen Bert M
Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Front Mol Neurosci. 2019 Nov 14;12:277. doi: 10.3389/fnmol.2019.00277. eCollection 2019.
The brain is a genomic mosaic. Cell-to-cell genomic differences, which are the result of somatic mutations during development and aging, contribute to cellular diversity in the nervous system. This genomic diversity has important implications for nervous system development, function, and disease. Brain somatic mosaicism might contribute to individualized behavioral phenotypes and has been associated with several neuropsychiatric and neurodegenerative disorders. Therefore, understanding the causes and consequences of somatic mosaicism in neural circuits is of great interest. Recent advances in 3D cell culture technology have provided new means to study human organ development and various human pathologies . Cerebral organoids ("mini-brains") are pluripotent stem cell-derived 3D culture systems that recapitulate, to some extent, the developmental processes and organization of the developing human brain. Here, I discuss the application of these neural organoids for modeling brain somatic mosaicism in a lab dish. Special emphasis is given to the potential role of microglial mutations in the pathogenesis of neurodegenerative diseases.
大脑是一个基因组镶嵌体。细胞间的基因组差异是发育和衰老过程中体细胞突变的结果，它促成了神经系统中的细胞多样性。这种基因组多样性对神经系统的发育、功能和疾病具有重要意义。大脑体细胞镶嵌现象可能导致个体行为表型的差异，并与多种神经精神疾病和神经退行性疾病相关。因此，了解神经回路中体细胞镶嵌现象的成因和后果具有重要意义。3D细胞培养技术的最新进展为研究人类器官发育和各种人类疾病提供了新方法。脑类器官（“微型大脑”）是多能干细胞衍生的3D培养系统，在一定程度上概括了发育中的人类大脑的发育过程和组织结构。在此，我将讨论这些神经类器官在实验室培养皿中模拟大脑体细胞镶嵌现象的应用。特别强调小胶质细胞突变在神经退行性疾病发病机制中的潜在作用。
