Adipogenic and SWAT cells separate from a common progenitor in human brown and white adipose depots
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Adipocyte function is a major determinant of metabolic disease, warranting investigations of regulating mechanisms. We show at single-cell resolution that progenitor cells from four human brown and white adipose depots separate into two main cell fates, an adipogenic and a structural branch, developing from a common progenitor. The adipogenic gene signature contains mitochondrial activity genes, and associates with genome-wide association study traits for fat distribution. Based on an extracellular matrix and developmental gene signature, we name the structural branch of cells structural Wnt-regulated adipose tissue-resident (SWAT) cells. When stripped from adipogenic cells, SWAT cells display a multipotent phenotype by reverting towards progenitor state or differentiating into new adipogenic cells, dependent on media. Label transfer algorithms recapitulate the cell types in human adipose tissue datasets. In conclusion, we provide a differentiation map of human adipocytes and define the multipotent SWAT cell, providing a new perspective on adipose tissue regulation.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature Metabolism |
| Vol/bind | 5 |
| Udgave nummer | 6 |
| Sider (fra-til) | 996-1013 |
| Antal sider | 18 |
| ISSN | 2522-5812 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank B. R. Lisdorf, M. Schrölkamp, T. J. Larsen, N. Mathur, P. Sandbeck and T. Hvidtfeldt Lorentzen for their technical assistance. We acknowledge The Single-Cell Omics platform at the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) for the technical expertise and support. We thank R. Barrés for providing initial RNA-seq. We acknowledge the Core Facility for Flow Cytometry and Single Cell Analysis, Faculty of Health and Medical Sciences, University of Copenhagen for their assistance with single-cell sorting for the clonal experiment. Parts of the computational analyses were performed using the Danish National Life Science Supercomputing Center, Computerome. CBMR is an independent Research Center, based at the University of Copenhagen and partially funded by an unconditional donation from the Novo Nordisk Foundation ( https://cbmr.ku.dk/ ; grant no. NNF18CC0034900). The Centre for Physical Activity Research is supported by a grant from TrygFonden (grant IDs 101390, 20045 and 125132). The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease is supported by a grant from the Novo Nordisk Foundation (NNF21SA0072102). We further acknowledge individual grants: P.N.T. was supported by an Elite Research PhD scholarship from the Danish Ministry of Higher Education and Science. N.Z.J. was supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation, grant no. NNF17SA0031406. T.H.P. was supported by grants from the Novo Nordisk Foundation (NNF16OC0021496) and Lundbeck Foundation (R19020143904). S.N. was supported by grants from the Novo Nordisk Foundation (NNF20OC0061400 and NNF18OC0052979). C.S. was supported by grants from Augustinus fonden (17-4359), Novo Nordisk Foundation (NNF15OC0017922) and Lundbeck foundation (2013-13799). This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101002725, to C.S.).
Funding Information:
We thank B. R. Lisdorf, M. Schrölkamp, T. J. Larsen, N. Mathur, P. Sandbeck and T. Hvidtfeldt Lorentzen for their technical assistance. We acknowledge The Single-Cell Omics platform at the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) for the technical expertise and support. We thank R. Barrés for providing initial RNA-seq. We acknowledge the Core Facility for Flow Cytometry and Single Cell Analysis, Faculty of Health and Medical Sciences, University of Copenhagen for their assistance with single-cell sorting for the clonal experiment. Parts of the computational analyses were performed using the Danish National Life Science Supercomputing Center, Computerome. CBMR is an independent Research Center, based at the University of Copenhagen and partially funded by an unconditional donation from the Novo Nordisk Foundation (https://cbmr.ku.dk/ ; grant no. NNF18CC0034900). The Centre for Physical Activity Research is supported by a grant from TrygFonden (grant IDs 101390, 20045 and 125132). The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease is supported by a grant from the Novo Nordisk Foundation (NNF21SA0072102). We further acknowledge individual grants: P.N.T. was supported by an Elite Research PhD scholarship from the Danish Ministry of Higher Education and Science. N.Z.J. was supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation, grant no. NNF17SA0031406. T.H.P. was supported by grants from the Novo Nordisk Foundation (NNF16OC0021496) and Lundbeck Foundation (R19020143904). S.N. was supported by grants from the Novo Nordisk Foundation (NNF20OC0061400 and NNF18OC0052979). C.S. was supported by grants from Augustinus fonden (17-4359), Novo Nordisk Foundation (NNF15OC0017922) and Lundbeck foundation (2013-13799). This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101002725, to C.S.).
Publisher Copyright:
© 2023, The Author(s).
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