High-resolution mouse subventricular zone stem-cell niche transcriptome reveals features of lineage, anatomy, and aging.
High-resolution mouse subventricular zone stem-cell niche transcriptome reveals features of lineage, anatomy, and aging.
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高分辨率小鼠室下区干细胞生态位转录组揭示了谱系、解剖学和衰老的特征。
DOI：
10.1073/pnas.2014389117
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发表时间：
2020
影响因子：
11.1
通讯作者：
Parada,LuisF
中科院分区：
文献类型：
--
作者：
Xie,XuanhuaP;Laks,DanR;Sun,Daochun;Poran,Asaf;Laughney,AshleyM;Wang,Zilai;Sam,Jessica;Belenguer,German;Fariñas,Isabel;Elemento,Olivier;Zhou,Xiuping;Parada,LuisF
成体神经干细胞（NSC）是脑可塑性的储存库，也是某些胶质瘤的起源。谱系追踪和基因组方法描绘了复杂的潜在的异质性内的主要解剖位置的NSC，脑室下区（SVZ）。为了获得NSC异质性的全面概况，我们利用了一种经过充分验证的干/祖细胞特异性报告基因与单细胞RNA测序相结合，以实现对SVZ细胞从婴儿期到老年的无偏分析。所得转录数据集的量级和高特异性允许精确鉴定嵌入SVZ中的各种细胞类型，包括专门的实质细胞（神经元、神经胶质细胞、小神经胶质细胞）和非中枢神经系统细胞（内皮细胞、免疫细胞）。初步挖掘的数据描绘了四个静止的神经干细胞和三个祖细胞亚群形成的线性进展。进一步的证据表明，不同的干细胞和祖细胞群体居住在SVZ的不同区域。随着干/祖细胞群体从新生儿到高龄的发展，它们在从静止到增殖的过渡中获得缺陷。进一步的数据挖掘确定了特定阶段的生物学过程，转录因子网络和细胞表面标志物，用于研究细胞身份，谱系关系和成年NSC维持和神经发生的关键调控途径。
Adult neural stem cells (NSC) serve as a reservoir for brain plasticity and origin for certain gliomas. Lineage tracing and genomic approaches have portrayed complex underlying heterogeneity within the major anatomical location for NSC, the subventricular zone (SVZ). To gain a comprehensive profile of NSC heterogeneity, we utilized a well-validated stem/progenitor-specific reporter transgene in concert with single-cell RNA sequencing to achieve unbiased analysis of SVZ cells from infancy to advanced age. The magnitude and high specificity of the resulting transcriptional datasets allow precise identification of the varied cell types embedded in the SVZ including specialized parenchymal cells (neurons, glia, microglia) and noncentral nervous system cells (endothelial, immune). Initial mining of the data delineates four quiescent NSC and three progenitor-cell subpopulations formed in a linear progression. Further evidence indicates that distinct stem and progenitor populations reside in different regions of the SVZ. As stem/progenitor populations progress from neonatal to advanced age, they acquire a deficiency in transition from quiescence to proliferation. Further data mining identifies stage-specific biological processes, transcription factor networks, and cell-surface markers for investigation of cellular identities, lineage relationships, and key regulatory pathways in adult NSC maintenance and neurogenesis.