Wnt signaling preserves progenitor cell multipotency during adipose tissue development

  • Nat Metab. 2023 Jun 19. doi: 10.1038/s42255-023-00813-y.
Zinger Yang Loureiro  1 ,  Shannon Joyce  1 ,  Tiffany DeSouza  2 ,  Javier Solivan-Rivera  1 ,  Anand Desai  2 ,  Pantos Skritakis  2 ,  Qin Yang  1 ,  Rachel Ziegler  2 ,  Denise Zhong  2 ,  Tammy T Nguyen  3  4 ,  Ormond A MacDougald  5  6 ,  Silvia Corvera  7  8
Affiliations
  • 1. Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • 2. Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • 3. Division of Vascular Surgery, Department of Surgery, UMass Memorial Medical Center, Worcester, MA, USA.
  • 4. Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • 5. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • 6. Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
  • 7. Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA. [email protected].
  • 8. Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA. [email protected].
PMID: 37337125 DOI: 10.1038/s42255-023-00813-y
Abstract

Mesenchymal stem/progenitor cells are essential for tissue development and repair throughout life, but how they are maintained under chronic differentiation pressure is not known. Using single-cell transcriptomics of human progenitor cells we find that adipose differentiation stimuli elicit two cellular trajectories: one toward mature adipocytes and another toward a pool of non-differentiated cells that maintain progenitor characteristics. These cells are induced by transient Wnt pathway activation and express numerous extracellular matrix genes and are therefore named structural Wnt-regulated adipose tissue cells. We find that the genetic signature of structural Wnt-regulated adipose tissue cells is present in adult human adipose tissue and adipose tissue developed from human progenitor cells in mice. Our results suggest a mechanism whereby adipose differentiation occurs concurrently with the maintenance of a mesenchymal progenitor cell pool, ensuring tissue development, repair and appropriate metabolic control over the lifetime.

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