Cellular Heterogeneity in Adipose Tissues

Abstract

Adipose tissue depots in distinct anatomical locations mediate key aspects of metabolism, including energy storage, nutrient release, and thermogenesis. Although adipocytes make up more than 90% of adipose tissue volume, they represent less than 50% of its cellular content. Here, I review recent advances in genetic lineage tracing and transcriptomics that reveal the identities of the heterogeneous cell populations constituting mouse and human adipose tissues. In addition to mature adipocytes and their progenitors, these include endothelial and various immune cell types that together orchestrate adipose tissue development and functions. One salient finding is the identification of progenitor subtypes that can modulate adipogenic capacity through paracrine mechanisms. Another is the description of fate trajectories of monocyte/macrophages, which can respond maladaptively to nutritional and thermogenic stimuli, leading to metabolic disease. These studies have generated an extraordinary source of publicly available data that can be leveraged to explore commonalities and differences among experimental models, providing new insights into adipose tissues and their role in metabolic disease.

Keywords: ADSC; adipocyte; adipokine; adipose-derived stem cell; adult stem cells; diabetes; obesity; progenitor cells.

Figure 1

Relative proportion of adipocytes in human subcutaneous and mouse inguinal adipose tissue depots as estimated by perilipin-1 (PLIN1) and DAPI (4′,6-diamidino-2-phenylindole) staining of whole-mount specimens. Analysis of human and mouse adipose tissue whole mounts stained with antibodies to PLIN1, with human or mouse isolectin to label the vasculature, and with DAPI to identify nuclei. Images represent maximal-intensity projections of 8 (human) or 6 (mouse) optical sections taken at 25-μm intervals. Grayscale images of PLIN1 and DAPI are shown, and the drawing was produced by the “analyze particles” algorithm in Fiji/ImageJ after thresholding. The numbers of objects representing either adipocytes or nuclei are shown. The percentages shown in parentheses represent the number of nuclei that correspond to adipocytes, whereas the remainder correspond to other cell types in the tissue.

Figure 2

Summary of findings and interpretations of transcriptomic studies of adipocytes, adipocyte progenitors, and immune cells in adipose tissue. Heterogeneous populations of cells identified in inguinal and perigonadal mouse adipose tissue or derived from human adipose tissue progenitors are illustrated. The names assigned to each subtype and the corresponding reference (superscripts) are shown, as are the genes associated with each population common between studies. The monocyte/macrophage trajectory reflects data in References 56 and 83–86.

Figure 3

Fates of mesenchymal progenitors isolated from diverse tissues reflect the cellular composition of vicinal structures.