Single-cell analysis of human adipose tissue identifies depot- and disease-specific cell types

Abstract

The complex relationship between metabolic disease risk and body fat distribution in humans involves cellular characteristics which are specific to body fat compartments. Here we show depotspecific differences in the stromal vascual fraction of visceral and subcutaneous adipose tissue by performing single-cell RNA sequencing of tissue specimen from obese individuals. We characterize multiple immune cells, endothelial cells, fibroblasts, adipose and hematopoietic stem cell progenitors. Subpopulations of adipose-resident immune cells are metabolically active and associated with metabolic disease status and those include a population of potential dysfunctional CD8+ T cells expressing metallothioneins. We identify multiple types of adipocyte progenitors that are common across depots, including a subtype enriched in individuals with type 2 diabetes. Depot-specific analysis reveals a class of adipocyte progenitors unique to visceral adipose tissue, *

Single-cell RNA-seq of the stromal vascular fraction of adipose tissue reveals lineage-specific changes in cancer-related lymphedema

“…The ASC lineage (marked by PDGFRA and DCN) (Guerrero-Juarez et al, 2019), including c0, c1, c3 and c5, accounted for a large proportion (49.2%) of the SVF ( Figure 1C), which is comparable with that (55%) reported previously (Vijay et al, 2020). A large and diverse population of immune cells (49.9%) were found, including both myeloid cells and lymphocytes.…”

“…Next, we found that the four subpopulations had distinct expression profiles ( Figure 3B; Table S3). Cluster c0 expressed high levels of adipose stem cell or preadipocyte markers such as CXCL14, APOD, APOE, MGP and WISP2 (Vijay et al, 2020). The gene signature of c0 was enriched with the Gene Ontology (GO) term "positive regulation of hemostasis" (representative genes: CD36, F3 and SELENOP; Figure 3C).…”

“…Adipose tissue is not simply a container of fat, but an endocrine organ, which is composed of multiple types of cells, such as adipose-derived stromal/stem/progenitor cells (ASCs), adipocytes, vascular cells (e.g., vascular endothelial cells and pericytes) and immune cells (e.g., macrophages and lymphocytes) (Vijay et al, 2020). All nonadipocyte cells are known as the stromal vascular fraction (SVF), which can be isolated through enzymatic digestion (Ramakrishnan and Boyd, 2018).…”

“…Single-cell RNA-seq is therefore emerging as a powerful tool for understanding the cellular and molecular mechanisms of pathogenesis in a variety of diseases such as pulmonary fibrosis (Reyfman et al, 2019) and lupus nephritis (Der et al, 2019). Single-4 / 40 cell RNA-seq has also been applied to dissect the heterogeneity of the SVF in mice (Burl et al, 2018;Schwalie et al, 2018) and humans (Vijay et al, 2020). However, to our knowledge, few studies have been performed to explore the alterations in the SVF under a diseased condition, for example, lymphedema, at a single-cell resolution.…”

Single-cell analysis reveals the pan-cancer invasiveness-associated transition of adipose-derived stromal cells into COL11A1-expressing cancer-associated fibroblasts

“…To demonstrate that the ASC population is naturally occurring in the normal adipose tissue of all types, we referred to recent results from single-cell analysis of general human adipose tissue (31). We found that one of the identified clusters (P5, table s2 of the paper 31 Therefore, to investigate the continuous transition of ASCs to COL11A1-expressing CAFs, we partitioned the 34 pancreatic samples into three groups, considering whether the corresponding attractor includes COL11A1 among the top 100 genes.…”