Human subcutaneous and visceral adipocyte atlases uncover classical and nonclassical adipocytes and depot-specific patterns
Or Lazarescu, Maya Ziv-Agam, Yulia Haim, Idan Hekselman, Juman Jubran, Ariel Shneyour, Habib Muallem, Alon Zemer, Marina Rosengarten-Levin, Daniel Kitsberg, Liron Levin, Idit F. Liberty, Uri Yoel, Oleg Dukhno, Miriam Adam, Julia Braune, Claudia Mueller, Nora Raulien, Martin Gericke, Antje Körner, Rinki Murphy, Matthias Blüher, Naomi Habib, Assaf Rudich, Esti Yeger‐Lotem
Abstract
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.