Toward a Consensus View of Mammalian Adipocyte Stem and Progenitor Cell Heterogeneity

• Published in: Trends in cell biology 2020-12, Vol.30 (12), p.937-950
• Main Authors: Ferrero, Radiana, Rainer, Pernille, Deplancke, Bart
• Format: Article
• Language: English
• Subjects: Adipocytes; adipogenesis; adipose stem cells; Adipose tissue; Cells (biology); Heterogeneity; Homeostasis; Mammals; mesothelial cells; obesity; Population structure; Progenitor cells; Regulatory mechanisms (biology); Resolution; single-cell RNA-seq; Stem cells
• ISSN: 0962-8924; 1879-3088
• DOI: 10.1016/j.tcb.2020.09.007

White adipose tissue (WAT) is a cellularly heterogeneous endocrine organ that not only serves as an energy reservoir, but also actively participates in metabolic homeostasis. Among the main constituents of adipose tissue are adipocytes, which arise from adipose stem and progenitor cells (ASPCs). While it is well known that these ASPCs reside in the stromal vascular fraction (SVF) of adipose tissue, their molecular heterogeneity and functional diversity is still poorly understood. Driven by the resolving power of single-cell transcriptomics, several recent studies provided new insights into the cellular complexity of ASPCs among different mammalian fat depots. In this review, we present current knowledge on ASPCs, their population structure, hierarchy, fat depot-specific nature, function, and regulatory mechanisms, and discuss not only the similarities, but also the differences between mouse and human ASPC biology. The adipose stem and progenitor cell (ASPC) fraction is heterogeneous and comprises at least three subpopulations: adipose stem cells (ASCs), preadipocytes (PreAs), and adipogenesis regulators (Aregs).ASCs (DPP4+, CD55+) give rise to both PreAs (ICAM1+, VAP-1+) and Aregs (CD142+).In adult mice, Aregs (CD142+) inhibit adipogenesis through paracrine mechanisms, which are not yet fully understood.In visceral fat, a subpopulation of ASCs, known as fibro inflammatory progenitors (FIPs) (PDGFRβ+/LY6C+), exerts an antiadipogenic effect.Mesothelial cells populate the stromal vascular fraction of visceral but not subcutaneous adipose tissue and modulate the immune environment.Human and mouse ASCs exhibit a common gene expression signature, but human PreAs and Aregs are molecularly less distinct than in mouse.ASPC heterogeneity differences between human and mouse question the full relevance of mouse ASPCs as an appropriate human adipose biology model system.