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

Martin Uhrbom (), Lars Muhl, Guillem Genové, Jianping Liu, Henrik Palmgren, Ida Alexandersson, Fredrik Karlsson, Alex-Xianghua Zhou, Sandra Lunnerdal, Sonja Gustafsson, Byambajav Buyandelger, Kasparas Petkevicius, Ingela Ahlstedt, Daniel Karlsson, Leif Aasehaug, Liqun He, Marie Jeansson, Christer Betsholtz () and Xiao-Rong Peng ()
Additional contact information
Martin Uhrbom: Neo building
Lars Muhl: Neo building
Guillem Genové: Neo building
Jianping Liu: Neo building
Henrik Palmgren: AstraZeneca
Ida Alexandersson: AstraZeneca
Fredrik Karlsson: R&D AstraZeneca
Alex-Xianghua Zhou: AstraZeneca
Sandra Lunnerdal: AstraZeneca
Sonja Gustafsson: Neo building
Byambajav Buyandelger: Neo building
Kasparas Petkevicius: AstraZeneca
Ingela Ahlstedt: AstraZeneca
Daniel Karlsson: AstraZeneca
Leif Aasehaug: AstraZeneca
Liqun He: Uppsala University
Marie Jeansson: Neo building
Christer Betsholtz: Neo building
Xiao-Rong Peng: AstraZeneca

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-51867-9

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