Single-Cell Transcriptomic Analysis of the Mouse Pancreas: Characteristic Features of Pancreatic Ductal Cells in Chronic Pancreatitis.
Single-Cell Transcriptomic Analysis of the Mouse Pancreas: Characteristic Features of Pancreatic Ductal Cells in Chronic Pancreatitis.
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DOI：
10.3390/genes13061015
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发表时间：
2022-06-05
期刊：
影响因子：
3.5
通讯作者：
Liao Z
中科院分区：
文献类型：
--
作者：
Mao X;Mao S;Wang L;Jiang H;Deng S;Wang Y;Ye J;Li Z;Zou W;Liao Z
慢性胰腺炎（CP）是一种胰腺纤维炎症性疾病。我们对 CP 发病机制的理解部分受到胰腺细胞类型不完整表征的限制。在这里，我们对来自一只对照小鼠和雨蛙素诱导的 CP 小鼠的胰腺的 3825 个细胞进行了单细胞 RNA 测序。对单细胞转录组的分析揭示了小鼠胰腺中 16 个独特的簇和细胞类型特异性基因表达模式。对对照小鼠的胰腺间充质细胞进行亚聚类，发现具有特定基因表达谱（Smoc2、Cxcl14、Tnfaip6 和 Fn1 的组合表达）的四个细胞簇。我们观察到 CP 小鼠胰腺中的免疫细胞丰富且细胞类型多样。与对照组相比，CP 组的导管细胞中有 547 个上调基因（包括 Mmp7、Ttr、Rgs5、Adh1 和 Cldn2）和 257 个下调基因。 CP患者胰管中MMP7和TTR表达水平的升高得到进一步验证。本研究初步描述了小鼠胰腺的单细胞转录组图谱，准确展示了CP中胰腺导管细胞的特征。这些发现提供了对新型疾病特异性生物标志物和 CP 潜在治疗靶点的见解。
Chronic pancreatitis (CP) is a fibroinflammatory disorder of the pancreas. Our understanding of CP pathogenesis is partly limited by the incomplete characterization of pancreatic cell types. Here, we performed single-cell RNA sequencing on 3825 cells from the pancreas of one control mouse and mice with caerulein-induced CP. An analysis of the single-cell transcriptomes revealed 16 unique clusters and cell type-specific gene expression patterns in the mouse pancreas. Sub-clustering of the pancreatic mesenchymal cells from the control mouse revealed four clusters of cells with specific gene expression profiles (combinatorial expressions of Smoc2, Cxcl14, Tnfaip6, and Fn1). We observed that immune cells in the pancreas of the CP mice were abundant and diverse in cellular type. Compared to the control, 547 upregulated genes (including Mmp7, Ttr, Rgs5, Adh1, and Cldn2) and 257 downregulated genes were identified in ductal cells from the CP group. The elevated expression levels of MMP7 and TTR were further verified in the pancreatic ducts of CP patients. This study provides a preliminary description of the single-cell transcriptome profiles of mouse pancreata and accurately demonstrates the characteristics of pancreatic ductal cells in CP. The findings provide insight into novel disease-specific biomarkers and potential therapeutic targets of CP.
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