Scholarlink

<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition impacting over 30% population, yet the dynamic changes in macrophage composition from steatosis to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH) remain unclear. Here, by integrating single-nucleus transcriptomics, spatial multi-omics and proteomics on human samples, we delineate the evolving landscape of hepatic macrophages across the MASLD spectrum. Our analysis reveals a progressive depletion of Kupffer cells accompanied by the emergence of diverse, phenotypically distinct macrophage subsets. Spatial multi-omics further demonstrates that disease progression toward MASH is marked by an accumulation of antigen-presenting, phagocytic GPNMB<sup>+</sup> macrophages, supported by IL32-producing hepatocytes. These macrophages showed an adaptive metabolic and pro-inflammatory phenotype that is tightly regulated by both spatial context and disease stage. Identified macrophage markers enable patient stratification by disease activity and its stage across independent clinical cohorts. Our study sheds light on the diversity of macrophage identities and metabolic-adaptive phenotypes during the progression of MASLD.</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

Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic dysfunction-associated steatohepatitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月18日

查看全文
  • Markus Boesch,
  • Seray Anak,
  • Dania El Abyad,
  • Tessa Ostyn,
  • Asier Antoranz,
  • Trieu My Van,
  • Daniel Newhouse,
  • Caitlyn Myers,
  • Lukas Van Melkebeke,
  • Jeremy Palmer,
  • Najmeh Saffarzadeh,
  • Jonathan Sai-Hong Chui,
  • Rita Feio-Azevedo,
  • Lena Smets,
  • Gautam Shankar,
  • Nikolina Dubroja Lakić,
  • Paula Longás Calvo,
  • Thierry Voet,
  • James Clark,
  • Simon Cockell,
  • Matthias Lannoo,
  • Ellen Deleus,
  • Joris Jaekers,
  • Halit Topal,
  • Baki Topal,
  • Kai Markus Schneider,
  • Michele Vacca,
  • Michael Allison,
  • Mattias Ekstedt,
  • Jerome Boursier,
  • Elisabetta Bugianesi,
  • Vlad Ratziu,
  • Frederik De Smet,
  • Bram Boeckx,
  • Ann K. Daly,
  • Jörn M. Schattenberg,
  • Jef Verbeek,
  • Francesca Bosisio,
  • Diether Lambrechts,
  • Tania Roskams,
  • Carolin V. Schneider,
  • Sven Francque,
  • Hannelie Korf,
  • Anetta Härtlova,
  • Dina Tiniakos,
  • Quentin M. Anstee,
  • Schalk van der Merwe,
  • Olivier Govaere

摘要

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition impacting over 30% population, yet the dynamic changes in macrophage composition from steatosis to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH) remain unclear. Here, by integrating single-nucleus transcriptomics, spatial multi-omics and proteomics on human samples, we delineate the evolving landscape of hepatic macrophages across the MASLD spectrum. Our analysis reveals a progressive depletion of Kupffer cells accompanied by the emergence of diverse, phenotypically distinct macrophage subsets. Spatial multi-omics further demonstrates that disease progression toward MASH is marked by an accumulation of antigen-presenting, phagocytic GPNMB+ macrophages, supported by IL32-producing hepatocytes. These macrophages showed an adaptive metabolic and pro-inflammatory phenotype that is tightly regulated by both spatial context and disease stage. Identified macrophage markers enable patient stratification by disease activity and its stage across independent clinical cohorts. Our study sheds light on the diversity of macrophage identities and metabolic-adaptive phenotypes during the progression of MASLD.