Scholarlink

<p>The primary cilium plays a crucial role in regulating whole-body energy metabolism, as reflected in Bardet-Biedl syndrome (BBS), where ciliary dysfunction leads to obesity due to hyperphagia and white adipose tissue (WAT) remodeling. Regulation of the fate and differentiation of adipocyte precursor cells (APCs) is essential for maintaining WAT homeostasis during obesity. Using <i>Bbs8</i><sup>−/−</sup> mice that recapitulate the BBS patient phenotype, we demonstrate that primary cilia dysfunction reduces the stem-cell-like P1 APC subpopulation by inducing a phenotypic switch to a fibrogenic progenitor state. This switch is characterized by extracellular matrix (ECM) remodeling and upregulation of the fibrosis marker CD9, even before the onset of obesity. Single-cell RNA sequencing reveals a direct transition of P1 APCs into fibrogenic progenitors, bypassing the committed P2 progenitor state. Ectopic ciliary Hedgehog signaling upon loss of BBS8 appears as a central driver of the molecular changes in <i>Bbs8</i><sup>−/−</sup> APCs, altering their differentiation into adipocytes and promoting their lipid uptake. These findings unravel a novel role for primary cilia in governing APC fate by determining the balance between adipogenesis and fibrogenesis, and suggest potential therapeutic targets for obesity.</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

BBS8-dependent ciliary Hedgehog signaling governs cell fate in the white adipose tissue

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月20日

查看全文
  • Katharina Sieckmann,
  • Nora Winnerling,
  • Dalila Juliana Silva Ribeiro,
  • Seniz Yüksel,
  • Ronja Kardinal,
  • Lisa Maria Steinheuer,
  • Fabian Frechen,
  • Luis Henrique Corrêa,
  • Geza Schermann,
  • Christina Klausen,
  • Nelli Blank-Stein,
  • Jonas Schulte-Schrepping,
  • Collins Osei-Sarpong,
  • Matthias Becker,
  • Lorenzo Bonaguro,
  • Marc Beyer,
  • Helen Louise May-Simera,
  • Jelena Zurkovic,
  • Christoph Thiele,
  • Kevin Thurley,
  • Lydia Sorokin,
  • Carmen Ruiz de Almodovar,
  • Elvira Mass,
  • Dagmar Wachten

摘要

The primary cilium plays a crucial role in regulating whole-body energy metabolism, as reflected in Bardet-Biedl syndrome (BBS), where ciliary dysfunction leads to obesity due to hyperphagia and white adipose tissue (WAT) remodeling. Regulation of the fate and differentiation of adipocyte precursor cells (APCs) is essential for maintaining WAT homeostasis during obesity. Using Bbs8−/− mice that recapitulate the BBS patient phenotype, we demonstrate that primary cilia dysfunction reduces the stem-cell-like P1 APC subpopulation by inducing a phenotypic switch to a fibrogenic progenitor state. This switch is characterized by extracellular matrix (ECM) remodeling and upregulation of the fibrosis marker CD9, even before the onset of obesity. Single-cell RNA sequencing reveals a direct transition of P1 APCs into fibrogenic progenitors, bypassing the committed P2 progenitor state. Ectopic ciliary Hedgehog signaling upon loss of BBS8 appears as a central driver of the molecular changes in Bbs8−/− APCs, altering their differentiation into adipocytes and promoting their lipid uptake. These findings unravel a novel role for primary cilia in governing APC fate by determining the balance between adipogenesis and fibrogenesis, and suggest potential therapeutic targets for obesity.