Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [scRNA-seq]

Here, we have used single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq) and spatial transcriptomics to characterize murine cortical OPCs throughout postnatal life. During development, we identify two differentially-localized PDGFRalpha-positive OPC populations that are transcriptionally and epigenetically distinct. One population (active or actOPCs) is metabolically active and is enriched in white matter. The second (homeostatic or hOPCs) is less active, enriched in grey matter, and predicted to derive from actOPCs. In adulthood, these two groups are transcriptionally but not epigenetically distinct, and relative to developing OPCs are less active metabolically with much less open chromatin. When adult oligodendrogenesis is enhanced following experimental demyelination, adult OPCs do not reacquire a developmental open chromatin state, and the oligodendrogenesis trajectory is distinct from that seen neonatally. These data support a model where two OPC populations subserve distinct postnatal functions, and where neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different. High-throughput single cell transcriptomic profiles of P2, P7, P15 and P60 from the mouse brain (SVZ and cortex) generated by single cell RNA sequencing using the 10X Genomics platform.本研究采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）、单细胞ATAC测序（single-cell ATAC sequencing, scATAC-seq）及空间转录组学技术，对小鼠出生后整个生命周期中的皮层少突胶质前体细胞（oligodendrocyte progenitor cells, OPCs）进行了系统表征。在发育进程中，我们鉴定出两个定位迥异且转录组与表观遗传特征均存在显著差异的PDGFRα阳性少突胶质前体细胞群：一类为激活型少突胶质前体细胞（active OPCs, actOPCs），其代谢活性较高，主要富集于白质区域；另一类为稳态型少突胶质前体细胞（homeostatic OPCs, hOPCs），代谢活性较低，主要富集于灰质区域，且推测其起源于actOPCs。 在成年阶段，这两类细胞仅在转录组层面存在差异，表观遗传层面则无显著区别；与发育阶段的少突胶质前体细胞相比，成年细胞代谢活性更低，开放染色质区域也显著减少。当实验性脱髓鞘后成年少突胶质生成过程增强时，成年少突胶质前体细胞并不会重新获得发育阶段的开放染色质状态，且其少突胶质生成轨迹与新生阶段存在本质差异。 本研究数据支持如下模型：两类少突胶质前体细胞分别承担出生后不同阶段的功能，且新生期与成年期由少突胶质前体细胞介导的少突胶质生成过程存在根本性差异。本数据集包含采用10X Genomics平台通过单细胞RNA测序获得的小鼠大脑（侧脑室下区（subventricular zone, SVZ）与皮层）在出生后第2天（P2）、第7天（P7）、第15天（P15）及第60天（P60）的高通量单细胞转录组图谱。