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A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion

Radiana Ferrero, Pernille Yde Rainer, Julie Russeil, Magda Zachara, Joern Pezoldt, Guido van Mierlo, Vincent Gardeux, Wouter Saelens, Daniel Alpern, Lucie Favre, Styliani Mantziari, Tobias Zingg, Nelly Pitteloud, Michel Suter, Maurice Matter, Carles Canto, Bart Deplancke
doi: https://doi.org/10.1101/2023.05.01.538871
Radiana Ferrero
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Pernille Yde Rainer
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Julie Russeil
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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Magda Zachara
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
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Joern Pezoldt
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Guido van Mierlo
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Vincent Gardeux
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Wouter Saelens
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Daniel Alpern
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Lucie Favre
3Department of Endocrinology, Diabetology and Metabolism, University Hospital of Lausanne (CHUV), CH-1011 Lausanne, Switzerland
5Faculty of Biology and Medicine, University of Lausanne, Lausanne, CH-1005 Switzerland
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Styliani Mantziari
4Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, CH-1011 Switzerland
5Faculty of Biology and Medicine, University of Lausanne, Lausanne, CH-1005 Switzerland
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Tobias Zingg
4Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, CH-1011 Switzerland
5Faculty of Biology and Medicine, University of Lausanne, Lausanne, CH-1005 Switzerland
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Nelly Pitteloud
3Department of Endocrinology, Diabetology and Metabolism, University Hospital of Lausanne (CHUV), CH-1011 Lausanne, Switzerland
5Faculty of Biology and Medicine, University of Lausanne, Lausanne, CH-1005 Switzerland
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Michel Suter
4Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, CH-1011 Switzerland
5Faculty of Biology and Medicine, University of Lausanne, Lausanne, CH-1005 Switzerland
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Maurice Matter
4Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, CH-1011 Switzerland
5Faculty of Biology and Medicine, University of Lausanne, Lausanne, CH-1005 Switzerland
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Carles Canto
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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Bart Deplancke
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
2Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
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  • For correspondence: bart.deplancke@epfl.ch
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Abstract

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). While several mouse and human adipose SVF cellular subpopulations have now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA-seq analyses of >30 Lin–SVF samples across four human adipose depots, revealing two ubiquitous hASPC subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2- expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 01, 2023.
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A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion
Radiana Ferrero, Pernille Yde Rainer, Julie Russeil, Magda Zachara, Joern Pezoldt, Guido van Mierlo, Vincent Gardeux, Wouter Saelens, Daniel Alpern, Lucie Favre, Styliani Mantziari, Tobias Zingg, Nelly Pitteloud, Michel Suter, Maurice Matter, Carles Canto, Bart Deplancke
bioRxiv 2023.05.01.538871; doi: https://doi.org/10.1101/2023.05.01.538871
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A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion
Radiana Ferrero, Pernille Yde Rainer, Julie Russeil, Magda Zachara, Joern Pezoldt, Guido van Mierlo, Vincent Gardeux, Wouter Saelens, Daniel Alpern, Lucie Favre, Styliani Mantziari, Tobias Zingg, Nelly Pitteloud, Michel Suter, Maurice Matter, Carles Canto, Bart Deplancke
bioRxiv 2023.05.01.538871; doi: https://doi.org/10.1101/2023.05.01.538871

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