小柯机器人

美国斯坦福大学Alexander E. Urban团队通过机器学习揭示人类神经元和神经胶质中体细胞L1插入的双边分布模式。相关论文于2021年1月11日在线发表在《自然—神经科学》杂志上。

通过使用机器学习方法（RetroSom）和深层全基因组测序，研究人员分析了人脑神经元和神经胶质中的L1和Alu逆转座。研究人员对精神分裂症供体神经元和神经胶质中的两个大脑特定L1插入进行了表征。L1插入在两个半球的神经元和神经胶质中呈解剖分布，这表明逆转座发生在早期胚胎发生期间。两种插入都在与神经精神疾病相关的基因组位点内的基因（CNNM2和FRMD4A）的内含子内。

实验表明，这些L1插入大大降低了基因表达。这些结果表明，RetroSom在脑发育研究中具有广泛的应用，并可能提供对体细胞逆转座的病理学见解。

据悉，逆转座子可引起人神经系统中的体细胞基因组变异，据推测与人类大脑发育和神经精神疾病有关。然而，人们对个体体细胞可移动元件插入的检测存在信噪比的问题。

附：英文原文

Title: Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia

Author: Xiaowei Zhu, Bo Zhou, Reenal Pattni, Kelly Gleason, Chunfeng Tan, Agnieszka Kalinowski, Steven Sloan, Anna-Sophie Fiston-Lavier, Jessica Mariani, Dmitri Petrov, Ben A. Barres, Laramie Duncan, Alexej Abyzov, Hannes Vogel, John V. Moran, Flora M. Vaccarino, Carol A. Tamminga, Douglas F. Levinson, Alexander E. Urban

Issue&Volume: 2021-01-11

Abstract: Retrotransposons can cause somatic genome variation in the human nervous system, which is hypothesized to have relevance to brain development and neuropsychiatric disease. However, the detection of individual somatic mobile element insertions presents a difficult signal-to-noise problem. Using a machine-learning method (RetroSom) and deep whole-genome sequencing, we analyzed L1 and Alu retrotransposition in sorted neurons and glia from human brains. We characterized two brain-specific L1 insertions in neurons and glia from a donor with schizophrenia. There was anatomical distribution of the L1 insertions in neurons and glia across both hemispheres, indicating retrotransposition occurred during early embryogenesis. Both insertions were within the introns of genes (CNNM2 and FRMD4A) inside genomic loci associated with neuropsychiatric disorders. Proof-of-principle experiments revealed these L1 insertions significantly reduced gene expression. These results demonstrate that RetroSom has broad applications for studies of brain development and may provide insight into the possible pathological effects of somatic retrotransposition. Zhu et al. discover that in human brain there is widespread anatomic distribution of low-frequency somatic, mosaic L1 insertions, using deep whole-genome sequencing of neuronal and glial fractions and machine-learning analysis.

DOI: 10.1038/s41593-020-00767-4

Source: https://www.nature.com/articles/s41593-020-00767-4

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex