Single-Cell Transcriptomes Reveal Characteristic Features of Mouse Hepatocytes with Liver Cholestatic Injury
Single-Cell Transcriptomes Reveal Characteristic Features of Mouse Hepatocytes with Liver Cholestatic Injury
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单细胞转录组揭示了肝胆汁淤积性损伤的小鼠肝细胞的特征
DOI：
10.3390/cells8091069
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发表时间：
2019-09-01
期刊：
影响因子：
6
通讯作者：
Li, Liying
中科院分区：
文献类型：
--
作者：
Chang, Na;Tian, Lei;Li, Liying
肝细胞是肝脏的主要实质细胞，在肝脏稳态和疾病过程中起着重要作用。正常肝细胞的异质性已被报道，但对肝胆汁淤积损伤中肝细胞的亚型和独特功能知之甚少。采用胆管结扎（BDL）诱导的小鼠肝损伤模型，进行单细胞RNA测序。Western blot和qPCR检测基因表达。采用免疫荧光法检测肝细胞中标记基因的表达。我们检测到一个表达细胞外基质基因的特异性肝细胞簇（BDL-6），表明这些肝细胞可能经历了上皮-间质转化。胆汁淤积损伤时，BDL-6的肝细胞也具有组织修复功能（如血管生成）。我们还发现四组胆汁淤积肝细胞（BDL-2、BDL-3、BDL-4和BDL-5）以不同的方式参与炎症过程。其中，BDL-2/3/5为炎症调节肝细胞，BDL-4为细胞趋化作用。在这四个集群中，BDL-5是特殊的。因为BDL-5的肝细胞是增殖性肝细胞。我们的分析提供了更多关于肝细胞在损伤肝脏中的独特功能的知识，并为未来针对肝细胞的治疗提供了基础。
Hepatocytes are the main parenchymal cells of the liver and play important roles in liver homeostasis and disease process. The heterogeneity of normal hepatocytes has been reported, but there is little knowledge about hepatocyte subtype and distinctive functions during liver cholestatic injury. Bile duct ligation (BDL)-induced mouse liver injury model was employed, and single-cell RNA sequencing was performed. Western blot and qPCR were used to study gene expression. Immunofluoresence was employed to detect the expressions of marker genes in hepatocytes. We detected a specific hepatocyte cluster (BDL-6) expressing extracellular matrix genes, indicating these hepatocytes might undergo epithelia-mesenchymal transition. Hepatocytes of BDL-6 also performed tissue repair functions (such as angiogenesis) during cholestatic injury. We also found that four clusters of cholestatic hepatocytes (BDL-2, BDL-3, BDL-4, and BDL-5) were involved in inflammatory process in different ways. To be specific, BDL-2/3/5 were inflammation-regulated hepatocytes, while BDL-4 played a role in cell chemotaxis. Among these four clusters, BDL-5 was special. because the hepatocytes of BDL-5 were proliferating hepatocytes. Our analysis provided more knowledge of hepatocyte distinctive functions in injured liver and gave rise to future treatment aiming at hepatocytes.