Spatial Transcriptomics of Adipose Tissue: Technologies, Applications, and Challenges

Abstract

Adipose tissue is a complex metabolic and endocrine organ that plays a central role in systemic energy homeostasis. While single-cell and single-nucleus RNA sequencing have revealed remarkable cellular heterogeneity within adipose tissue depots, these approaches lack spatial context, limiting the ability to understand how cellular organization and microenvironmental cues shape adipose tissue biology. Spatial transcriptomics (ST) has emerged as a powerful technology to overcome this barrier by allowing one to map gene expression directly within intact tissue sections. Recent advances in ST platforms now permit analysis at a high resolution, enabling interrogation of adipocyte subpopulations, stromal progenitors, immune cell infiltration, and tissue remodeling. In this review, we provide an overview of current ST technologies, computational strategies for analysis, and recent applications for understanding adipose tissue biology. We further highlight key opportunities for ST to address unanswered questions surrounding adipogenic niches, depot-specific remodeling, and immune cell interactions. Together, these advances position ST as a transformative tool for dissecting the architecture and function of adipose tissue in health and metabolic disease.

Keywords: Adipose tissue; Cell plasticity; Gene expression profiling; Spatial analysis.

Figure 1

Graphical representation of spatial phenomena in white (left) and brown (right) adipose tissue. A, lipid-associated macrophages (red) surrounding a dying adipocyte in a CLS; B, white adipocyte undergoing beiging process; C, heterogeneous gene expression in mature adipocytes; D, receptor/ligand interactions; E, interstitial adipose stromal cell (ASC); F, perivascular ASC; and G, immune/ASC interactions.

Figure 2

A simplified comparison of sequencing versus imaging-based spatial transcriptomics. In general, sequencing-based techniques (left) entail applying sectioned tissue to a scaffold/slide containing barcoded ‘spots’ so that the RNA is captured with a unique barcode corresponding to the area of tissue it came from. cDNA is synthesized from these barcoded oligos and subsequentially sequenced, resulting in a gene x location matrix. Imaging-based (right) techniques typically involve applying fluorescent probes to sectioned tissue in a targeted manner to directly target genes of interest. Several rounds of imaging take place and the fluorescent signal and location of probes is then compiled into a gene×location matrix. 3D, three dimensional; 2D, two dimensional.