A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure.
A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure.
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DOI：
10.1016/j.cels.2016.08.011
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发表时间：
2016-10-26
期刊：
影响因子：
9.3
通讯作者：
Yanai I
中科院分区：
文献类型：
--
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
虽然哺乳动物胰腺的功能取决于不同细胞类型的复杂相互作用，但基因表达谱主要是用散装混合物描述的。在这里，我们实施了一种基于液滴的单细胞RNA-seq方法，以确定来自四个人类供体和两个小鼠品系的超过12，000个单个胰腺细胞的转录组。细胞可以分为15个簇，与先前表征的细胞类型相匹配：所有内分泌细胞类型，包括罕见的ε细胞;外分泌细胞类型;血管细胞;许旺细胞;静止和活化的星状细胞;和四种类型的免疫细胞。我们检测到不同的表达谱的导管细胞亚群，并验证其存在与免疫组化染色。此外，在人类β细胞中，我们检测到与功能成熟和ER应激水平相关的基因调节的异质性。最后，我们使用单细胞数据对大量基因表达样本进行去卷积，以检测疾病相关的差异表达。我们的数据集为发现新的细胞类型特异性转录因子，信号受体和医学相关基因提供了资源。使用inDrop确定了来自四个人类供体和两个小鼠品系的超过12，000个细胞的单细胞转录组学。细胞被分成15个簇，与先前表征的细胞类型相匹配。对每个群体的详细分析分别揭示了导管群体内的亚群、星状细胞的激活模式以及β细胞之间的应激异质性。
Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes. Single-cell transcriptomics of over 12,000 cells from four human donors and two mouse strains was determined using inDrop. Cells were divided into 15 clusters that matched previously characterized cell types. Detailed analysis of each population separately revealed subpopulations within the ductal population, modes of activation of stellate cells, and heterogeneity in the stress among beta cells.