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Lazarescu, O.* ; Ziv-Agam, M.* ; Haim, Y.* ; Hekselman, I.* ; Jubran, J.* ; Shneyour, A.* ; Muallem, H.* ; Zemer, A.* ; Rosengarten-Levin, M.* ; Kitsberg, D.* ; Levin, L.* ; Liberty, I.F.* ; Yoel, U.* ; Dukhno, O.* ; Adam, M.* ; Braune, J.* ; Müller, C.* ; Raulien, N.* ; Gericke, M.* ; Körner, A. ; Murphy, R.* ; Blüher, M. ; Habib, N.* ; Rudich, A.* ; Yeger-Lotem, E.*

Human subcutaneous and visceral adipocyte atlases uncover classical and nonclassical adipocytes and depot-specific patterns.

Nat. Genet. 57, 413-426 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA sequencing (snRNA-seq) analyses largely uncovered overlapping or similar cell-type landscapes. We hypothesized that adipocyte subtypes, differentiation trajectories and/or intercellular communication patterns could illuminate this depot similarity-difference gap. For this, we performed snRNA-seq of human subcutaneous or visceral adipose tissues (five or ten samples, respectively). Of 27,665 adipocyte nuclei in both depots, most were 'classical', namely enriched in lipid metabolism pathways. However, we also observed 'nonclassical' adipocyte subtypes, enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization or angiogenesis or ribosomal and mitochondrial processes. Pseudo-temporal analysis showed a developmental trajectory from adipose progenitor cells to classical adipocytes via nonclassical adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Last, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation and intercellular communication patterns to human fat depot differences.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Adipose-tissue; Obesity; Matrix; Stem; Fat
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 57, Issue: 2, Pages: 413-426 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Chan Zuckerberg Initiative Foundation, grant CZIF2019-002441
Chan Zuckerberg Initiative Foundation - Deutsche Forschungsgemeinschaft (German Research Foundation)
Myers Foundation