Single-nucleus analysis of human white adipose tissue reveals adipocyte subsets with distinct metabolic profiles
Abstract
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.
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BibTeX
@article{efthymiou2026singlenucleus,
title = {{Single-nucleus analysis of human white adipose tissue reveals adipocyte subsets with distinct metabolic profiles}},
author = {Vissarion Efthymiou and Adhideb Ghosh and Sean Kodani and Habib Muallem and Xavier Caubit and Waqar Ali and Lindsay Poulos and Henrique Camara and Anushka Gupta and Yasmine Belaidouni and A. Sina Booeshaghi and Shiyi Yang and Ruchir Rastogi and Farnaz Shamsi and Ashley Vernon and Laurent Fasano and Assaf Rudich and Aaron Streets and Yu-Hua Tseng and Mary Elizabeth Patti},
journal = {Nature Communications},
year = {2026},
month = aug,
doi = {10.1038/s41467-026-75426-6},
url = {https://hal.science/hal-05764286v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Single-nucleus analysis of human white adipose tissue reveals adipocyte subsets with distinct metabolic profiles
AU - Vissarion Efthymiou
AU - Adhideb Ghosh
AU - Sean Kodani
AU - Habib Muallem
AU - Xavier Caubit
AU - Waqar Ali
AU - Lindsay Poulos
AU - Henrique Camara
AU - Anushka Gupta
AU - Yasmine Belaidouni
AU - A. Sina Booeshaghi
AU - Shiyi Yang
AU - Ruchir Rastogi
AU - Farnaz Shamsi
AU - Ashley Vernon
AU - Laurent Fasano
AU - Assaf Rudich
AU - Aaron Streets
AU - Yu-Hua Tseng
AU - Mary Elizabeth Patti
PY - 2026
DA - 2026/08/05
JO - Nature Communications
DO - 10.1038/s41467-026-75426-6
UR - https://hal.science/hal-05764286v1
AB - 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.
SN - 2041-1723
SN - 2041-1723
ER -