肝脏再生的细胞和分子调控机制

肝脏是脊椎动物的重要消化器官，其受损后的再生修复与人口健康密切相关。与其它器官相比，肝脏具有较强的再生能力。揭示肝脏再生的细胞来源即内源性肝脏前体细胞/干细胞及其发挥功能的分子机制具有重要的基础和临床意义。本项目拟以斑马鱼为模式动物，通过建立斑马鱼肝脏损伤再生模型，致力于鉴定在肝脏再生修复过程中发挥关键作用的内源性肝脏前体细胞，并揭示肝脏前体细胞发挥修复功能的细胞和分子机制。本项目包括以下六项研究内容：1）斑马鱼肝脏损伤再生模型的建立；2）参与斑马鱼肝脏再生的内源性肝脏前体细胞的鉴定；3）斑马鱼肝脏前体细胞在肝脏损伤再生过程中的细胞行为和功能研究；4）斑马鱼肝脏再生的ENU正向遗传诱变筛选及致变基因的定位克隆；5）肝脏再生重要调控基因的增强子捕获研究；6）重要致变基因和捕获基因在肝脏再生中的功能和作用机制研究。

The liver is an essential digestive organ in vertebrate. It is well-known that it has fascinating regenerative capacity after toxic or mechanical injuries. Identities of endogenous liver stem/progenitor cells that play part in regeneration are of great scientific and clinical interest. By establishing zebrafish liver regeneration model, this project is aiming to identify the hepatic progenitors pivotal for liver regeneration and reveal their cellular and molecular mechanisms. This project is divided into six parts: 1) Establishment of liver injury and regeneration model in zebrafish. 2) Identification of endogenous liver progenitor cells using our zebrafish model. 3) Cellular behavior and functional studies of liver progenitors during the liver injury and regeneration processes. 4) ENU forward genetic screen for liver regeneration and positional cloning of mutated genes. 5) Enhancer trap for key regulatory genes of liver regeneration. 6) Roles and molecular mechanisms of mutated or trapped genes in liver regeneration.