Scholarlink

<p>The liver’s regenerative ability depends on injury extent. Minor injuries are repaired by hepatocyte self-duplication, while severe damage triggers cholangiocyte involvement in hepatocyte recovery. This paradigm is well-documented for adult animals but is less explored during rapid growth. We design two partial liver injury models in zebrafish, which were investigated during growth spurts: 1) partial ablation, killing half the hepatocytes; and 2) partial hepatectomy, removing half a liver lobe. In both injuries, de novo hepatocytes emerged alongside existing ones. Single-cell transcriptomics and lineage tracing with Cre-driver lines generated by genome editing identified cholangiocytes as the source of de novo hepatocytes. We further identify active mTORC1 signalling in the uninjured liver of growing animal to be a regulator of the enhanced plasticity of cholangiocytes. Our study suggests cholangiocyte-to-hepatocyte transdifferentiation as the primary mechanism of liver regeneration during periods of rapid growth.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Cholangiocytes contribute to hepatocyte regeneration after partial liver injury during growth spurt in zebrafish

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月6日

查看全文
  • Sema Elif Eski,
  • Jiarui Mi,
  • Macarena Pozo-Morales,
  • Gabriel Garnik Hovhannisyan,
  • Camille Perazzolo,
  • Rita Manco,
  • Imane Ez-Zammoury,
  • Dev Barbhaya,
  • Anne Lefort,
  • Frédérick Libert,
  • Federico Marini,
  • Esteban N. Gurzov,
  • Olov Andersson,
  • Sumeet Pal Singh

摘要

The liver’s regenerative ability depends on injury extent. Minor injuries are repaired by hepatocyte self-duplication, while severe damage triggers cholangiocyte involvement in hepatocyte recovery. This paradigm is well-documented for adult animals but is less explored during rapid growth. We design two partial liver injury models in zebrafish, which were investigated during growth spurts: 1) partial ablation, killing half the hepatocytes; and 2) partial hepatectomy, removing half a liver lobe. In both injuries, de novo hepatocytes emerged alongside existing ones. Single-cell transcriptomics and lineage tracing with Cre-driver lines generated by genome editing identified cholangiocytes as the source of de novo hepatocytes. We further identify active mTORC1 signalling in the uninjured liver of growing animal to be a regulator of the enhanced plasticity of cholangiocytes. Our study suggests cholangiocyte-to-hepatocyte transdifferentiation as the primary mechanism of liver regeneration during periods of rapid growth.