Species and Cell-Type Properties of Classically Defined Human and Rodent Neurons and Glia [Rat ATAC-Seq]

Determination of the molecular properties of genetically targeted cell types has led to fundamental insights into mouse brain function and dysfunction. Here, we report an efficient strategy for precise exploration of gene expression events in specific cell types in a broad range of species. We demonstrate that classically defined, homologous neuronal and glial cell types differ between rodent and human by the expression of hundreds of orthologous, cell specific genes. Confirmation that these genes are differentially active was obtained using epigenetic mapping, quantitative PCR, and immunofluorescence localization. Studies of sixteen human postmortem brains revealed cell-specific molecular responses to aging, and the induction of a shared, robust response to an unknown external event experienced by three donors. Our data establish a comprehensive approach for analysis of unique molecular events associated with specific circuits and cell types in a wide variety of human conditions.对经遗传靶向标记的细胞类型的分子特性进行解析，已为我们理解小鼠脑的功能与功能异常带来了基础性认知。本研究报道了一种高效策略，可精准探究广泛物种类群中特定细胞类型内的基因表达事件。研究证实，经典定义的同源神经元与胶质细胞类型，在啮齿类与人类之间存在数百个直系同源细胞特异性基因的表达差异。通过表观遗传图谱分析、定量聚合酶链式反应（quantitative PCR）以及免疫荧光定位实验，验证了这些基因的活性存在差异。对16例人类死后脑组织的研究显示，细胞类型特异性的分子应答随衰老发生变化；同时有3例脑供体的细胞共同产生了针对未知外界刺激的强烈共有应答反应。本研究的数据确立了一套全面的分析方法，可用于解析多种人类生理与病理状态下，与特定神经环路及细胞类型相关的独特分子事件。