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Characterization of the adipocyte cellular lineage in vivo

Nature Cell Biology volume 15, pages 302–308 (2013)Cite this article

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Abstract

Mature adipocytes are generated through the proliferation and differentiation of precursor cells. Our previous studies identified adipocyte progenitors in white adipose tissue (WAT) as Lin−:CD29+:CD34+:Sca-1+:CD24+ (CD24+) cells that are capable of generating functional WAT (ref. 1). Here, we employ several Cre recombinase mouse models to identify the adipocyte cellular lineage in vivo. Although it has been proposed that white adipocytes are derived from endothelial2 and haematopoietic3,4 lineages, we find that neither of these lineages label white adipocytes. However, platelet-derived growth factor receptor α (PdgfR α)–Cre trace labels all white adipocytes. Analysis of WAT from PdgfR α–Cre reporter mice identifies CD24+ and Lin−:CD29+:CD34+:Sca-1+: CD24− (CD24−) cells as adipocyte precursors. We show that CD24+ cells generate the CD24− population in vivo and the CD24− cells express late markers of adipogenesis. From these data we propose a model where the CD24+ adipocyte progenitors become further committed to the adipocyte lineage as CD24 expression is lost, generating CD24− preadipocytes. This characterization of the adipocyte cellular lineage will facilitate the study of the mechanisms that regulate WAT formation in vivo and WAT mass expansion in obesity.

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Figure 1: Adipocytes are derived from PdgfRα+ precursor cells in subcutaneous WAT.
Figure 2: CD24+ adipocyte progenitors give rise to CD24− cells in vivo.
Figure 3: CD24− cells express late adipogenic genes.
Figure 4: CD24− cells are further committed to an adipogenic fate.

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Acknowledgements

We thank E. Jeffery, C. Church, D. Krause and V. Horsley for critical reading of the manuscript and valuable discussions. This work was supported by American Diabetes Association Award 7-12-JF-46, DERC pilot project grant DK045735 and NIDDK grant DK090489 to M.S.R. and NIDDK grant DK041096 to J. M. Friedman.

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Authors and Affiliations

  1. Department of Molecular, Cell and Developmental Biology, School of Medicine, Yale University, New Haven, Connecticut 06520, 375 Congress Avenue, USA

    Ryan Berry & Matthew S. Rodeheffer

  2. Section of Comparative Medicine, School of Medicine, Yale University, 375 Congress Avenue, New Haven, Connecticut 06520, USA

    Matthew S. Rodeheffer

  3. Yale Stem Cell Center, Yale University, 06520, USA

    Matthew S. Rodeheffer

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  1. Ryan Berry
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R.B. and M.S.R. designed and performed experiments, analysed and interpreted data and wrote the manuscript.

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Correspondence to Matthew S. Rodeheffer.

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Berry, R., Rodeheffer, M. Characterization of the adipocyte cellular lineage in vivo. Nat Cell Biol 15, 302–308 (2013). https://doi.org/10.1038/ncb2696

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