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<p>Anatomic location of white adipose tissue is a determinant of cardiometabolic risk. To understand differences within/between adipose depots, we generated 65,668 single-nucleus transcriptomes from human subcutaneous or intraabdominal adipose tissue (SAT/IAT). Unsupervised analysis reveals 26 adipose-resident cell clusters including two subpopulations of mature adipocytes, characterized by high vs. low expression of adipocyte maturation genes (ADIPOMAT<sup>hi</sup> vs. ADIPOMAT<sup>lo</sup>). ADIPOMAT<sup>lo</sup> adipocytes demonstrate a low-differentiation, pro-inflammatory, and pro-fibrotic transcriptome. IAT-resident ADIPOMAT<sup>lo</sup> were more abundant in higher BMI donors, while SAT-resident ADIPOMAT<sup>lo</sup> associated with impaired glycemia. TSHZ3 is identified as a candidate regulator of ADIPOMAT<sup>lo</sup> transcriptome. TSHZ3 knockdown in adipogenic progenitors inhibits differentiation, with downregulation of early adipogenic regulators (e.g., CEBPA/B, PPARG) and mature adipocyte genes. Heterozygous deletion of <i>Tshz3</i> in mice reduces SAT and IAT weight. Here, we show that adipocyte subsets with distinct transcriptomic signature reside in human WAT; altered TSHZ3-mediated transcriptional regulation may contribute to low-maturation subpopulation linked to metabolic disease.</p>

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Single-nucleus analysis of human white adipose tissue reveals adipocyte subsets with distinct metabolic profiles

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Vissarion Efthymiou,
  • Adhideb Ghosh,
  • Sean D. Kodani,
  • Habib Muallem,
  • Xavier Caubit,
  • Waqar Ali,
  • Lindsay S. Poulos,
  • Henrique Camara,
  • Anushka Gupta,
  • Yasmine Belaidouni,
  • A. Sina Booeshaghi,
  • Shiyi Yang,
  • Ruchir Rastogi,
  • Farnaz Shamsi,
  • Ashley Vernon,
  • Laurent Fasano,
  • Assaf Rudich,
  • Aaron Streets,
  • Yu-Hua Tseng,
  • Mary Elizabeth Patti

摘要

Anatomic location of white adipose tissue is a determinant of cardiometabolic risk. To understand differences within/between adipose depots, we generated 65,668 single-nucleus transcriptomes from human subcutaneous or intraabdominal adipose tissue (SAT/IAT). Unsupervised analysis reveals 26 adipose-resident cell clusters including two subpopulations of mature adipocytes, characterized by high vs. low expression of adipocyte maturation genes (ADIPOMAThi vs. ADIPOMATlo). ADIPOMATlo adipocytes demonstrate a low-differentiation, pro-inflammatory, and pro-fibrotic transcriptome. IAT-resident ADIPOMATlo were more abundant in higher BMI donors, while SAT-resident ADIPOMATlo associated with impaired glycemia. TSHZ3 is identified as a candidate regulator of ADIPOMATlo transcriptome. TSHZ3 knockdown in adipogenic progenitors inhibits differentiation, with downregulation of early adipogenic regulators (e.g., CEBPA/B, PPARG) and mature adipocyte genes. Heterozygous deletion of Tshz3 in mice reduces SAT and IAT weight. Here, we show that adipocyte subsets with distinct transcriptomic signature reside in human WAT; altered TSHZ3-mediated transcriptional regulation may contribute to low-maturation subpopulation linked to metabolic disease.