Novel insights into adipose tissue heterogeneity
Tóm tắt
When normalized to volume, adipose tissue is comprised mainly of large lipid metabolizing and storing cells called adipocytes. Strikingly, the numerical representation of non-adipocytes, composed of a wide variety of cell types found in the so-called stromal vascular fraction (SVF), outnumber adipocytes by far. Besides its function in energy storage, adipose tissue has emerged as a versatile organ that regulates systemic metabolism and has therefore constituted an attractive target for the treatment of metabolic diseases. Recent high-resolution single cells/nucleus RNA seq data exemplify an intriguingly profound diversity of both adipocytes and SVF cells in all adipose depots, and the current data, while limited, demonstrate the significance of the intra-tissue cell composition in shaping the overall functionality of this tissue. Due to the complexity of adipose tissue, our understanding of the biological relevance of this heterogeneity and plasticity is fractional. Therefore, establishing atlases of adipose tissue cell heterogeneity is the first step towards generating an understanding of these functionalities. In this review, we will describe the current knowledge on adipose tissue cell composition and the heterogeneity of single-cell RNA sequencing, including the technical limitations.
Tài liệu tham khảo
Vigarello G. The metamorphoses of fat: a history of obesity. Columbia University Press. 2013. https://doi.org/10.7312/viga15976.
Vaisse C, et al. Leptin activation of Stat3 in the hypothalamus of wild–type and ob/ob mice but not db/db mice. Nat Genet. 1996;14:95–7.
Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011;121:2094–101.
Stephens JM. The fat controller: adipocyte development. PLoS Biol. 2012;10:e1001436.
Pi-Sunyer X. The medical risks of obesity. Postgrad Med. 2009;121:21–33.
Longo M, et al. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. Int J Mol Sci. 2019;20:2358.
Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders. Front Endocrinol. 2016;7.
Rondini EA, Granneman JG. Single cell approaches to address adipose tissue stromal cell heterogeneity. Biochem J. 2020;477:583–600.
Sell H, Deshaies Y, Richard D. The brown adipocyte: update on its metabolic role. Int J Biochem Cell Biol. 2004;36:2098–104.
Rosenwald M, Perdikari A, Rülicke T, Wolfrum C. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol. 2013;15:659–67.
Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med. 2013;19:1338–44.
Rodeheffer MS, Birsoy K, Friedman JM. Identification of white adipocyte progenitor cells in vivo. Cell. 2008;135:240–9.
Tang W, et al. White fat progenitor cells reside in the adipose vasculature. Science. 2008;322:583–6.
Berry DC, Jiang Y, Graff JM. Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function. Nat Commun. 2016;7:10184.
Lee YH, Petkova AP, Mottillo EP, Granneman JG. In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high-fat feeding. Cell Metab. 2012;15:480–91.
Long JZ, et al. A smooth muscle-like origin for beige adipocytes. Cell Metab. 2014;2014(19):810–20.
Vishvanath L, et al. Pdgfrβ+ mural preadipocytes contribute to adipocyte hyperplasia induced by high-fat-diet feeding and prolonged cold exposure in adult mice. Cell Metab. 2016;23:350–9.
Berry R, Jeffery E, Rodeheffer MS. Weighing in on Adipocyte Precursors. Cell Metab. 2014;19:8–20.
Chappell L, Russell AJC, Voet T. Single-cell (Multi)omics technologies. Annu Rev Genomics Hum Genet. 2018;19:15–41.
Liu S, Trapnell C. Single-cell transcriptome sequencing: recent advances and remaining challenges. F1000Research. 2016;5:182.
Slyper M, et al. A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors. Nat Med. 2020;26:792–802.
Schwalie PC, et al. A stromal cell population that inhibits adipogenesis in mammalian fat depots. Nature. 2018;559:103–8.
Merrick D, et al. Identification of a mesenchymal progenitor cell hierarchy in adipose tissue. Science. 2019;364:eaav2501.
Camps J, et al. Interstitial cell remodeling promotes aberrant adipogenesis in dystrophic muscles. Cell Rep. 2020;31:107597.
Hepler C, et al. Identification of functionally distinct fibro- inflammatory and adipogenic stromal subpopulations in visceral adipose tissue of adult mice. Elife. 2018;7:e39636.
Oguri Y, et al. CD81 controls beige fat progenitor cell growth and energy balance via FAK Signaling. Cell. 2020;182:563-577.e20.
Angueira AR, et al. Defining the lineage of thermogenic perivascular adipose tissue. Nat Metab. 2021;3:469–84.
Russo L, Lumeng CN. Properties and functions of adipose tissue macrophages in obesity. Immunology. 2018;155:407–17.
Thomas D, Apovian C. Macrophage functions in lean and obese adipose tissue. Metabolism. 2017;72:120–43.
Vishvanath L, Gupta RK. Contribution of adipogenesis to healthy adipose tissue expansion in obesity. J Clin Invest. 2019;129:4022–31.
Vijay J, et al. Single-cell analysis of human adipose tissue identifies depot- and disease-specific cell types. Nat Metab. 2020;2:97–109.
Olefsky J, Saltiel A. PPARγ and the treatment of insulin resistance. Trends Endocrinol Metab. 2000;11:362–8.
Burl RB, et al. Deconstructing adipogenesis induced by β3-adrenergic receptor activation with single-cell expression profiling. Cell Metab. 2018;28:300–309.e4.
Rajbhandari P, et al. Single cell analysis reveals immune cell– adipocyte crosstalk regulating the transcription of thermogenic adipocytes. Elife. 2019;8:e49501.
Sun W, et al. snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis. Nature. 2020;587:98–102.
Sárvári AK, et al. Plasticity of epididymal adipose tissue in response to diet-induced obesity at single-nucleus resolution. Cell Metab. 2020;S1550413120306598. https://doi.org/10.1016/j.cmet.2020.12.004.
Richardson D, Czech M. Diminished activities of fatty acid synthesis enzymes in insulin-resistant adipocytes from spontaneously obese rats. Horm Metab Res. 1979;11:427–31.
Hagberg CE, et al. Flow cytometry of mouse and human adipocytes for the analysis of browning and cellular heterogeneity. Cell Rep. 2018;24:2746-2756.e5.
Matthews BG, Ono N, Kalajzic I. Methods in lineage tracing. Princi Bone Biol. Elsevier, 2020;1887–1898. https://doi.org/10.1016/B978-0-12-814841-9.00081-6.
Wagner DE, Klein AM. Lineage tracing meets single-cell omics: opportunities and challenges. Nat Rev Genet. 2020;21:410–27.