Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
Miller School of Medicine, University of Miami, Miami, United States.
Elife. 2018 Oct 15;7:e37551. doi: 10.7554/eLife.37551.
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 and epigenetic events in specific cell types in a range of species, including postmortem human brain. 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 and immunofluorescence localization. Studies of sixteen human postmortem brains revealed gender specific transcriptional differences, cell-specific molecular responses to aging, and the induction of a shared, robust response to an unknown external event evident in three donor samples. Our data establish a comprehensive approach for analysis of molecular events associated with specific circuits and cell types in a wide variety of human conditions.
对基因靶向细胞类型的分子特性的测定，使我们深入了解了老鼠大脑的正常和异常功能。在这里，我们报告了一种在多种物种（包括人死后的大脑）中精确探索特定细胞类型中基因表达和表观遗传事件的有效策略。我们证明，在啮齿动物和人类中，通过数百个同源的、细胞特异性的基因的表达，经典定义的同源神经元和神经胶质细胞类型存在差异。通过表观遗传图谱和免疫荧光定位，证实了这些基因的差异活性。对 16 个人类死后大脑的研究揭示了性别特异性转录差异、细胞对衰老的特定分子反应，以及在三个供体样本中明显的、共同的强烈反应诱导。我们的数据建立了一种全面的方法，用于分析与广泛的人类疾病中的特定回路和细胞类型相关的分子事件。
