Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development.

Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development.
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DOI:
10.1016/j.devcel.2018.07.005
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发表时间:
2018-08-20
期刊:
影响因子:
11.8
通讯作者:
Castelo-Branco G
Castelo-Branco G
中科院分区:
生物学1区
文献类型:
--
作者:
Marques S;van Bruggen D;Vanichkina DP;Floriddia EM;Munguba H;Väremo L;Giacomello S;Falcão AM;Meijer M;Björklund ÅK;Hjerling-Leffler J;Taft RJ;Castelo-Branco G

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Pdgfra+少突胶质细胞前体细胞(OPCs)在中枢神经系统(CNS)的胚胎发生期间以不同的特化波出现。目前还不清楚这些波和不同的少突胶质细胞(OL)在成年阶段的状态之间是否存在相关性。在这里,我们提出了大量和单细胞转录组学资源,提供了关于这些状态之间如何发生转换的见解。我们发现,出生后的OPCs从大脑和脊髓呈现相似的转录签名。此外,出生后的OPC后代E13.5 Pdgfra+细胞的电生理和转录谱类似的OPC衍生自随后的规范波,表明Pdgfra+前OPC重新布线他们的转录网络在发展过程中。单细胞RNA-seq和谱系追踪表明,E13.5 Pdgfra+细胞的子集起源于周细胞谱系的细胞。因此,我们的研究结果表明,胚胎Pdgfra+细胞在中枢神经系统中产生不同的出生后细胞谱系,包括在不同的中枢神经系统区域具有收敛的转录谱的OPC。来源于CNS不同部位的OPCs彼此高度相似,前OPCs会聚成相似的转录和电生理OPC状态E13.5 Pdgfra+细胞主要在出生后CNS中产生OPCs E13.5 Pdgfra+细胞也产生周细胞谱系的细胞Marques,货车Bruggen,Vanichkina等。提供了胚胎和出生后阶段小鼠前脑和脊髓Pdgfra+细胞的大量和单细胞转录组学资源。胚胎Pdgfra+细胞产生不同的出生后细胞谱系。出生后的少突胶质细胞前体细胞来自不同的中枢神经系统区域最终是高度相似的。
Pdgfra+ oligodendrocyte precursor cells (OPCs) arise in distinct specification waves during embryogenesis in the central nervous system (CNS). It is unclear whether there is a correlation between these waves and different oligodendrocyte (OL) states at adult stages. Here, we present bulk and single-cell transcriptomics resources providing insights on how transitions between these states occur. We found that post-natal OPCs from brain and spinal cord present similar transcriptional signatures. Moreover, post-natal OPC progeny of E13.5 Pdgfra+ cells present electrophysiological and transcriptional profiles similar to OPCs derived from subsequent specification waves, indicating that Pdgfra+ pre-OPCs rewire their transcriptional network during development. Single-cell RNA-seq and lineage tracing indicates that a subset of E13.5 Pdgfra+ cells originates cells of the pericyte lineage. Thus, our results indicate that embryonic Pdgfra+ cells in the CNS give rise to distinct post-natal cell lineages, including OPCs with convergent transcriptional profiles in different CNS regions. OPCs arising from different parts of the CNS are highly similar to one another Pre-OPCs converge into similar transcriptional and electrophysiological OPC states E13.5 Pdgfra+ cells give rise mainly to OPCs in the post-natal CNS E13.5 Pdgfra+ cells also give rise to cells of the pericyte lineage Marques, van Bruggen, Vanichkina et al. present a bulk and single-cell transcriptomics resource of mouse forebrain and spinal cord Pdgfra+ cells at embryonic and post-natal stages. Embryonic Pdgfra+ cells produce distinct post-natal cell lineages. Post-natal oligodendrocyte precursor cells arising from different CNS regions are ultimately highly similar.
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