The adipose tissue cell type enriched transcriptome

Adipose tissue (fat) is a highly specialized loose connective tissue composed primarily of adipocytes. It has a range of physiological functions, such as the insulation and protection of organs, the storage of energy, and secretion of metabolic hormones; indeed, it is increasingly considered a central metabolic organ in the regulation of whole-body energy homeostasis. Fat is mainly located either around the organs (visceral adipose tissue) or beneath the skin (subcutaneous adipose tissue).

2356 genes were predicted to have cell type specificity in visceral adipose tissue, and 1980 genes were predicted to have cell type specificity in subcutaneous adipose tissue.

Visceral adipose tissue

  • 10 cell types profiled
  • 926 very highly enriched genes
  • 622 highly enriched genes
  • 808 moderately enriched genes

Subcutaneous adipose tissue

  • 8 cell types profiled
  • 929 very highly enriched genes
  • 591 highly enriched genes
  • 460 moderately enriched genes

Adipose tissue cell type enriched transcriptome: Summary

Genes with predicted cell type specificity within visceral or subcutaneous adipose tissue are detailed below (Table 1 and 2, respectively). Identified enriched genes are subdivided into 3 specificity categories, based on the difference between the enrichment score in the corresponding cell type, compared to the other cell types profiled in the tissue (see Methods Summary page for details):

  • Predicted specificity: ´Very high´ - Differential score vs. other profiled cell types within the tissue >0.35
  • Predicted specificity: ´High´ - Differential score vs. other profiled cell types within the tissue >0.25
  • Predicted specificity: ´Moderate´ - Differential score vs. other profiled cell types within the tissue >0.15


Table 1. Number of genes in each specificity category in the visceral adipose cell types.

Cell type Very highHighModerate Total enriched
Adipocytes (Visceral) 462 69 26 557
Mesothelial cells 137 152 127 416
Endothelial cells 46 65 104 215
Smooth muscle cells 57 32 28 117
Adipose progenitor cells 11 56 284 351
Macrophages 78 72 72 222
Neutrophils 34 17 13 64
Mast cells 4 6 6 16
T-cells 18 100 132 250
Plasma cells 79 53 16 148
All cell types 926622808 2356

Figure 1. Bar plot of the number of enriched genes in the cell types of the visceral adipose tissue, divided by specificity category

Table 2. Number of genes in each specificity categoriy in the subcutaneous adipose cell types.

Cell type Very highHighModerate Total enriched
Adipocytes (Subcutaneous) 515 70 20 605
Endothelial cells 67 57 43 167
Smooth muscle cells 156 95 80 331
Adipose progenitor cells 25 112 103 240
Macrophages 117 116 107 340
Mast cells 13 8 15 36
T-cells 10 71 80 161
Plasma cells 26 62 12 100
All cell types 929591460 1980

Figure 2. Bar plot of the number of enriched genes in the cell types of the subcutaneous adipose tissue, divided by specificity category

Adipose tissue cell type enriched transcriptome: Illustrative examples

Adipocytes

Adipocytes are the predominant cell type found in adipose tissue. The mature adipocyte has several tasks, the most obvious being storage of lipids as an energy depot and metabolism of these lipids according to systemic needs. The lipids are stored as lipid droplets, that contribute to the cells’ high buoyancy, large size and round shape. Adipocytes also secrete several important signaling molecules, known as adipokines. Through adipokine secretion, adipocytes play an important role in regulating the energy balance and metabolic pathways in the body.

The active processes of lipogenesis and lipolysis in adipocytes is reflected by the high expression of lipid metabolic pathway genes, such as Acyl-CoA Synthetase Long Chain Family Member 1 (ACSL1), and other accessory molecules, such as Perilipin 4 (PLIN4), which coats lipid droplets to protect them from lipases. Protein Kinase CAMP-Dependent Type II Regulatory Subunit Beta (PRKAR2B), a signaling regulatory subunit involved in adipocyte maturation, and Microsomal Glutathione S-Transferase 1 (MGST1), an antioxidant enzyme that protects cells from lipid peroxidation, were also classified as having specificity in adipocytes in both visceral and subcutaneous adipose tissue.


ACSL1 - Adipose subcutaneous

ACSL1

PLIN4 - Adipose subcutaneous

PLIN4

PRKAR2B - Adipose subcutaneous

PRKAR2B

MGST1 - Adipose subcutaneous

MGST1

Adipose progenitor cells

Adipose progenitor cells are a transient cell type, with characteristics of both mesenchymal/fibroblastic cells and adipocytes. Adipose progenitor cells is a broad term, with cells in this category covering multiple developmental stages within the adipogenic pathway. These cells resemble an early stage of adipocyte development, before markers of stem cells or multipotent progenitors are lost following differentiation.

Genes classified as having specificity in adipose progenitor cells include Mannose Receptor C Type 2 (MRC2), which plays a role in extracellular matrix remodeling, Cadherin 11 (CDH11), which plays a role in calcium-dependent cell-cell adhesion, as well as genes with unknown function such as Deleted In Primary Ciliary Dyskinesia Homolog (DPCD).


MRC2 - Adipose subcutaneous

MRC2

CDH11 - Adipose subcutaneous

CDH11

Mesothelial cells

Mesothelial cells form a flattened and squamous monolayer that line both the serosal cavities and the organs within. They have several protective functions, including creating a low friction surface so that organs can move freely, as well as protecting organs within the cavity by transporting required molecules and cells across the serous membrane, while keeping microbes and other potential dangers out. They have also been found to be involved in inflammatory responses and wound healing, in addition to expressing pro- and anti -coagulant factors. In adipose tissue, mesothelial cells have only been identified in visceral depots and seem to be absent in subcutaneous depots.

Mesothelial cells are of mesoderm origin, and genes classified as having specificity include keratins such as KRT8 and KRT19, kallikreins such as KLK7 and KLK8, as well as genes related to coagulation such as the anticoagulant protein Annexin A8 (ANXA8).


KRT8 - Adipose visceral

KLK7 - Adipose visceral

ANXA8 - Adipose visceral

The immunohistochemistry images of adipose tissue featured in the Human Protein Atlas do not currently include examples from the greater omentum section of the visceral peritoneum.

Relevent publications

Norreen-Thorsen M et al., A human adipose tissue cell-type transcriptome atlas. Cell Rep. (2022)
PubMed: 35830816 DOI: 10.1016/j.celrep.2022.111046