We present a nuclei isolation protocol for genomic and epigenomic interrogation of multiple cell type populations in the human and rodent brain. The nuclei isolation protocol allows cell type-specific profiling of neurons, microglia, oligodendrocytes, and astrocytes, being compatible with fresh and frozen samples obtained from either resected or postmortem brain tissue. This 2-day procedure consists of tissue homogenization with fixation, nuclei extraction, and antibody staining followed by fluorescence-activated nuclei sorting (FANS) and does not require specialized skillsets. Cell type-specific nuclei populations can be used for downstream omic-scale sequencing applications with an emphasis on epigenomic interrogation such as histone modifications, transcription factor binding, chromatin accessibility, and chromosome architecture. The nuclei isolation protocol enables translational examination of archived healthy and diseased brain specimens through utilization of existing medical biorepositories.

我们提出了一种核分离方案，用于对人类和啮齿动物大脑中的多种细胞类型群进行基因组和表观基因组的询问。细胞核分离协议允许对神经元、小胶质细胞、少突胶质细胞和星形胶质细胞进行细胞类型特异性分析，与从切除或死后脑组织获得的新鲜和冷冻样本兼容。这个为期 2 天的程序包括组织均质化、固定、细胞核提取和抗体染色，然后是荧光激活细胞核分选 (FANS)，不需要专门的技能。细胞类型特异性细胞核群可用于下游组学规模测序应用，重点是表观基因组询问，例如组蛋白修饰、转录因子结合、染色质可及性和染色体结构。