A survey of human brain transcriptome diversity at the single cell level.
A survey of human brain transcriptome diversity at the single cell level.
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DOI：
10.1073/pnas.1507125112
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发表时间：
2015-06-09
影响因子：
11.1
通讯作者：
Quake SR
中科院分区：
文献类型：
--
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
大脑由大量的细胞和细胞连接组成。据我们所知，我们描述了第一次对人类成人皮质样本进行的单细胞全转录组分析。我们已经建立了一个实验和分析框架，可以在单细胞水平上解剖人脑的复杂性。使用这种方法，我们能够识别大脑的所有主要细胞类型，并表征神经元细胞的亚型。我们观察到的变化，神经元从早期发育到晚期分化阶段的成人。我们发现一个子集的成年神经元表达主要组织相容性复合体I类基因，因此没有免疫特权。人类大脑是一个非常复杂的组织，就其所包含的细胞类型而言。以单细胞分辨率对人脑中的细胞类型进行分类的常规方法限于探索相对较少的标记物，因此提供了任何给定细胞类型的有限分子表征。我们在466个细胞上使用单细胞RNA测序，以在整个转录组水平上捕获成人和胎儿人脑的细胞复杂性。在外科手术过程中获得健康成人颞叶组织，其中在患有医学难治性癫痫发作的患者中移除其他正常组织以获得更深的海马病理学。我们能够将单个细胞分类为大脑中所有主要的神经元、神经胶质和血管细胞类型。我们能够将神经元分成单独的社区，并表明这些社区保留了通常使用经典的中间神经元标记物观察到的中间神经元亚型的分类。然后，我们使用单细胞RNA测序胎儿人皮质神经元，以确定基因之间的差异表达的胎儿和成人神经元和那些显示的表达梯度，反映了复制和静止的胎儿神经元群体之间的过渡的基因。最后，我们观察到的主要组织相容性复合体I型基因的表达在一个子集的成人神经元，但不是胎儿神经元。这里提出的工作证明了单细胞RNA测序在成人大脑研究中的适用性，并构成了人类大脑全面细胞图谱的第一步。
The brain comprises an immense number of cells and cellular connections. We describe the first, to our knowledge, single cell whole transcriptome analysis of human adult cortical samples. We have established an experimental and analytical framework with which the complexity of the human brain can be dissected on the single cell level. Using this approach, we were able to identify all major cell types of the brain and characterize subtypes of neuronal cells. We observed changes in neurons from early developmental to late differentiated stages in the adult. We found a subset of adult neurons which express major histocompatibility complex class I genes and thus are not immune privileged. The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.
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影响因子：
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作者：
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通讯作者：
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