Department of Biochemistry, YLL School of Medicine, National University of Singapore, Singapore, 119615, Singapore.
Laboratory of Human Diseases and Immunotherapies, West China Hospital, Sichuan University, 610041, Chengdu, China.
Commun Biol. 2020 Nov 3;3(1):642. doi: 10.1038/s42003-020-01364-8.
The liver and gallbladder are among the most important internal organs derived from the endoderm, yet the development of the liver and gallbladder in the early embryonic stages is not fully understood. Using a transgenic Foxa2 reporter mouse line, we performed single-cell full-length mRNA sequencing on endodermal and hepatic cells isolated from ten embryonic stages, ranging from E7.5 to E15.5. We identified the embryonic liver developmental trajectory from gut endoderm to hepatoblasts and characterized the transcriptome of the hepatic lineage. More importantly, we identified liver primordium as the nascent hepatic progenitors with both gut and liver features and documented dynamic gene expression during the epithelial-hepatic transition (EHT) at the stage of liver specification during E9.5-11.5. We found six groups of genes switched on or off in the EHT process, including diverse transcripitional regulators that had not been previously known to be expressed during EHT. Moreover, we identified and revealed transcriptional profiling of gallbladder primordium at E9.5. The present data provides a high-resolution resource and critical insights for understanding the liver and gallbladder development.
肝脏和胆囊是源自内胚层的最重要的内部器官之一，但早期胚胎阶段肝脏和胆囊的发育还不完全清楚。我们使用一种转基因 Foxa2 报告鼠系，对源自从 E7.5 到 E15.5 的十个胚胎阶段的内胚层和肝细胞进行了单细胞全长 mRNA 测序。我们确定了从肠内胚层到肝前体细胞的胚胎肝脏发育轨迹，并对肝谱系的转录组进行了特征描述。更重要的是，我们发现肝原基是具有肠和肝特征的新生肝祖细胞，并在 E9.5-11.5 的肝脏特化阶段的上皮-肝转化（EHT）过程中记录了动态基因表达。我们发现 EHT 过程中有六组基因被开启或关闭，其中包括先前未知在 EHT 期间表达的多种转录调节因子。此外，我们还鉴定并揭示了 E9.5 时胆囊原基的转录谱。本数据提供了一个高分辨率的资源，并为理解肝脏和胆囊的发育提供了关键的见解。
