Glia-specific nuclei isolation and single cell transcriptomics inform astrocyte pathology in human temporal lobe epilepsy

The role of human glia in many neurological disorders is still poorly understood due to the lack of tools that reliably isolate specific glial subpopulations from bulk tissue, directly from their native niche. To better understand the contributions of glial pathology in human epilepsy, we developed and validated a novel sorting strategy that simultaneously isolates nuclei populations of astrocytes (PAX6+), oligodendroglial progenitors (OPCs) (OLIG2+) and neurons (NEUN+) from non-pathological fresh-frozen human postmortem temporal neocortex brain tissue (TL Control) and then employed it, in combination with single cell RNA-seq, to characterize the cell-type specific transcriptome alterations in epilepsy temporal neocortex derived from fresh surgical material in patients with medically refractory temporal lobe epilepsy (TLE). The provided Metadata file contains exhaustive information on the different types of processed data provided herein, and the protocols used to generate it. Please not that due to space constriction, the raw FASTQ data are only provided to the GEO (currently submitted in folder "GEO_Epilepsy:nadiats", review in process, to be released immediately after review).由于缺乏能够直接从天然微环境中、从大块组织内可靠分离特定胶质细胞亚群的工具，人类胶质细胞在多种神经系统疾病中的作用仍未得到充分阐明。为了更好地阐释胶质细胞病理改变在人类癫痫中的贡献，我们开发并验证了一种新型分选策略，该策略可同时从非病变新鲜冰冻人类尸检颞新皮层组织（TL对照组）中分离出星形胶质细胞（astrocytes，PAX6+）、少突胶质细胞祖细胞（oligodendroglial progenitors, OPCs，OLIG2+）以及神经元（neurons，NEUN+）的细胞核群体；随后将该策略与单细胞RNA测序（single cell RNA-seq）相结合，对来源于药物难治性颞叶癫痫（TLE）患者的新鲜手术标本的癫痫颞新皮层组织进行细胞类型特异性转录组特征分析。本数据集附带的元数据文件（Metadata file）包含了本文所提供的各类处理后数据的详尽信息，以及生成这些数据所使用的实验方案。请注意，由于存储空间限制，原始FASTQ数据仅提交至GEO数据库（目前已上传至文件夹"GEO_Epilepsy:nadiats"，审核流程正在进行中，审核通过后将立即公开）。