Department of Clinical Neurosciences, Laboratory of Neurotherapies and Neuromodulation (LNTM), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neuroscience Research Center, LNTM, Lausanne University Hospital, 1011 Lausanne, Switzerland.
Department of Physiology, Laboratory of Neuroenergetics, University of Lausanne, 1005 Lausanne, Switzerland.
Cell Rep. 2019 Feb 26;26(9):2477-2493.e9. doi: 10.1016/j.celrep.2019.02.003.
The role of brain cell-type-specific functions and profiles in pathological and non-pathological contexts is still poorly defined. Such cell-type-specific gene expression profiles in solid, adult tissues would benefit from approaches that avoid cellular stress during isolation. Here, we developed such an approach and identified highly selective transcriptomic signatures in adult mouse striatal direct and indirect spiny projection neurons, astrocytes, and microglia. Integrating transcriptomic and epigenetic data, we obtained a comprehensive model for cell-type-specific regulation of gene expression in the mouse striatum. A cross-analysis with transcriptomic and epigenomic data generated from mouse and human Huntington's disease (HD) brains shows that opposite epigenetic mechanisms govern the transcriptional regulation of striatal neurons and glial cells and may contribute to pathogenic and compensatory mechanisms. Overall, these data validate this less stressful method for the investigation of cellular specificity in the adult mouse brain and demonstrate the potential of integrative studies using multiple databases.
脑细胞特异性功能和特征在病理和非病理环境中的作用仍未得到充分定义。在实体、成年组织中，这种细胞特异性基因表达谱将受益于避免细胞分离过程中应激的方法。在这里，我们开发了这样一种方法，并鉴定了成年小鼠纹状体直接和间接棘突投射神经元、星形胶质细胞和小胶质细胞中的高度选择性转录组特征。整合转录组和表观遗传数据，我们获得了一个用于小鼠纹状体中基因表达细胞特异性调控的综合模型。与从小鼠和亨廷顿病 (HD) 大脑生成的转录组和表观遗传数据的交叉分析表明，相反的表观遗传机制控制着纹状体神经元和神经胶质细胞的转录调控，可能有助于致病和代偿机制。总的来说，这些数据验证了这种对成年小鼠大脑中细胞特异性进行研究的应激较小的方法，并展示了使用多个数据库进行综合研究的潜力。
