The Impact of Single-Cell Genomics on Adipose Tissue Research

Abstract

<jats:p>Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to dissect tissue heterogeneity through the transcriptional characterization of individual cells, is responsible for facilitating critical advancements in this area. The unique investigative capabilities achieved by the combination of nanotechnology, molecular biology, and informatics are expanding our understanding of adipose tissue’s composition and compartmentalized functional specialization, which underlie physiologic and pathogenic states, including adaptive thermogenesis, adipose tissue aging, and obesity. In this review, we will summarize the use of scRNA-seq and single-nuclei RNA-seq (snRNA-seq) in adipocyte biology and their applications to obesity and diabetes research in the hopes of increasing awareness of the capabilities of this technology and acting as a catalyst for its expanded use in further investigation.</jats:p>

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

“…Interestingly, in vivo models of beige adipogenesis revealed a depot-selective heterogeneity of APCs in their potential to transform toward beige adipocytes, suggesting an influence of the local microenvironment [ 19 ]. Single-cell genomics studies have significantly improved our understanding of the developmental origin and regulatory pathways of beige adipocyte progenitors [ 20 ]. These studies identified CD81 (Cluster of Differentiation 81) as a highly selective marker for the beige APCs.…”

Chemically Defined Xeno- and Serum-Free Cell Culture Medium to Grow Human Adipose Stem Cells

“…Initially, Rodeheffer et al identified and Berry et al characterized a subpopulation of early adipocyte progenitors defined as CD24 + CD29 + CD34 + Sca-1 (Ly6A) + in mouse WAT [ 31 , 129 ]. Since then, many studies have found distinct adipocyte progenitor cells with various cell surface proteins expressed in WAT [ 128 ] and, recently, single-cell RNA sequencing (scRNAseq) technology was used to find new gene markers able to better define the cellular subpopulation involved in adipogenesis (reviewed in [ 130 , 131 ]). This new way to search for new markers led David Merrick et al [ 45 ] to identify distinct types of progenitor cells in murine subcutaneous adipose tissue, which were subdivided into three hierarchical groups based on their gene expression patterns (reviewed in [ 132 , 133 ]).…”

Characterization of transcript enrichment and detection bias in single-nuclei RNA-seq for mapping of distinct human adipocyte lineages

“…Consequently, recent studies are beginning to elucidate cellular heterogeneity and developmental pathways in distinct adipose tissue lineages at the single-cell level (Deutsch et al 2020;Ferrero et al 2020).…”

“…Primary adipocytes can be difficult to work with due to their fragile nature, high buoyancy, and large size (Deutsch et al 2020). Existing protocols for tissue digestion and single-cell suspension preparation often result in complete or partial adipocyte lysis and therefore are not compatible with scRNA-seq library preparation.…”