Single-cell approaches define two groups of mammalian oligodendrocyte precursor cells and their evolution over developmental time.

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cell Reports Pub Date : 2024-05-14 Epub Date: 2024-04-04 DOI:10.1016/j.stemcr.2024.03.002
Daniel J Dennis, Beatrix S Wang, Konstantina Karamboulas, David R Kaplan, Freda D Miller
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Abstract

Here, we used single-cell RNA sequencing (scRNA-seq), single-cell ATAC sequencing (scATAC-seq), and single-cell spatial transcriptomics to characterize murine cortical OPCs throughout postnatal life. During development, we identified two groups of differentially localized PDGFRα+ OPCs that are transcriptionally and epigenetically distinct. One group (active, or actOPCs) is metabolically active and enriched in white matter. The second (homeostatic, or hOPCs) is less active, enriched in gray 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 and have less open chromatin. When adult oligodendrogenesis is enhanced during experimentally induced remyelination, adult OPCs do not reacquire a developmental open chromatin state, and the oligodendrogenesis trajectory is distinct from that seen neonatally. These data suggest that there are two OPC groups subserving distinct postnatal functions and that neonatal and adult OPC-mediated oligodendrogenesis are fundamentally different.

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单细胞方法确定了哺乳动物少突胶质前体细胞的两个组别及其随发育时间的演变。
在这里,我们利用单细胞 RNA 测序(scRNA-seq)、单细胞 ATAC 测序(scATAC-seq)和单细胞空间转录组学研究了小鼠皮质 OPC 在整个出生后的特征。在发育过程中,我们发现了两组不同定位的 PDGFRα+ OPCs,它们在转录和表观遗传方面各不相同。其中一组(活跃OPCs)新陈代谢活跃,富集在白质中。第二组(homeostatic,或称 hOPCs)活性较低,富含于灰质中,预计来自于 actOPCs。在成年期,这两组细胞在转录上有区别,但在表观遗传上没有区别,与发育中的 OPCs 相比,它们的新陈代谢不那么活跃,染色质的开放程度也较低。在实验诱导的再髓鞘化过程中,当成年少突胶质细胞生成增强时,成年 OPCs 不会重新获得发育期的开放染色质状态,而且少突胶质细胞生成轨迹与新生儿期不同。这些数据表明,有两个 OPC 群体在出生后发挥着不同的功能,而且新生儿和成年 OPC 介导的少突形成有着本质区别。
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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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