Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [scMultiome-seq]. Single cell approaches define two mammalian oligodendrocyte precursor cell populations and their evolution over developmental time [scMultiome-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 PDGFRα-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. Overall design: High-throughput single cell transcriptomic profiles of P6 from the mouse brain (SVZ) generated by single cell multiome 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）进行表征。在发育过程中，我们鉴定出两个定位分布不同的PDGFRα阳性少突胶质前体细胞群体，二者在转录组与表观遗传层面均存在显著差异。其中一类群体（激活型少突胶质前体细胞，active or actOPCs）代谢活性旺盛，富集于白质区域；另一类群体（稳态型少突胶质前体细胞，homeostatic or hOPCs）活性较低，富集于灰质区域，且推测起源于actOPCs。
在成年阶段，这两类群体仅在转录组层面存在差异，表观遗传层面并无显著区别；相较于发育阶段的少突胶质前体细胞，成年群体代谢活性更低，开放染色质区域也显著减少。当实验性脱髓鞘诱导成年少突胶质生成增强时，成年少突胶质前体细胞并未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显著差异。
本研究数据支持如下模型：两类少突胶质前体细胞群体分别执行不同的出生后功能，且新生期与成年期少突胶质前体细胞介导的少突胶质生成过程存在本质差异。
整体实验设计：采用10X Genomics平台的单细胞多组测序技术，构建小鼠出生后第6天（postnatal day 6, P6）脑室下区（subventricular zone, SVZ）脑组织的高通量单细胞转录组图谱。