Adipose stem cells are sexually dimorphic cells with dual roles as preadipocytes and resident fibroblasts

• Published in: Nature communications Vol. 15; no. 1; pp. 7643 - 19
• Main Authors: Uhrbom, Martin, Muhl, Lars, Genové, Guillem, Liu, Jianping, Palmgren, Henrik, Alexandersson, Ida, Karlsson, Fredrik, Zhou, Alex-Xianghua, Lunnerdal, Sandra, Gustafsson, Sonja, Buyandelger, Byambajav, Petkevicius, Kasparas, Ahlstedt, Ingela, Karlsson, Daniel, Aasehaug, Leif, He, Liqun, Jeansson, Marie, Betsholtz, Christer, Peng, Xiao-Rong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.09.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/31; 14/1; 14/19; 38/39; 38/91; 631/443/319/2723; 631/532/2118/2074; 631/80; Adipocytes - cytology; Adipocytes - metabolism; Adipogenesis - genetics; Adipose tissue; Adipose Tissue - cytology; Adipose Tissue - metabolism; Aldosterone; Angiotensin; Animals; Body fat; Cell Differentiation; Environmental factors; Estrogens; Extracellular matrix; Extracellular Matrix - metabolism; Female; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Homeobox; Humanities and Social Sciences; Humans; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Microvasculature; multidisciplinary; Position (location); Preadipocytes; Renin; Science; Science (multidisciplinary); Sex Characteristics; Sex hormones; Sexual dimorphism; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-51867-9

Cell identities are defined by intrinsic transcriptional networks and spatio-temporal environmental factors. Here, we explored multiple factors that contribute to the identity of adipose stem cells, including anatomic location, microvascular neighborhood, and sex. Our data suggest that adipose stem cells serve a dual role as adipocyte precursors and fibroblast-like cells that shape the adipose tissue’s extracellular matrix in an organotypic manner. We further find that adipose stem cells display sexual dimorphism regarding genes involved in estrogen signaling, homeobox transcription factor expression and the renin-angiotensin-aldosterone system. These differences could be attributed to sex hormone effects, developmental origin, or both. Finally, our data demonstrate that adipose stem cells are distinct from mural cells, and that the state of commitment to adipogenic differentiation is linked to their anatomic position in the microvascular niche. Our work supports the importance of sex and microvascular function in adipose tissue physiology. Several factors contribute to the identity of adipose stem cells, including anatomic location, microvascular neighborhood and sex. Here, authors find that adipose stem cells are sexual dimorphic cells with dual roles as preadipocytes and fibroblasts.