Spatial Transcriptomic Analysis of Human Visceral Adipose Tissue in Different Metabolic Status: Methodological...

Area of Science:

• Transcriptomics
• Spatial Biology
• Adipose Tissue Biology

Background:

• Adipose tissue's lipid-rich adipocytes challenge spatial transcriptomic analysis.
• Spatially-resolved laser-activated cell sorting (SLACS) offers precise tissue section isolation for transcriptomics.

Purpose of the Study:

• To investigate spatial transcriptomic differences in human visceral adipose tissue (VAT).
• To analyze cellular composition and post-transcriptional regulation in distinct VAT areas.
• To explore potential contributors to adipose tissue dysfunction in obesity and type 2 diabetes mellitus (Ob-DM).

Main Methods:

• Human VAT samples from lean and Ob-DM individuals were analyzed.
• SLACS was employed to isolate perivascular (PV) and adipocyte-rich (AD) areas.
• Full-length RNA sequencing was performed on isolated areas.

Main Results:

• PV and AD areas showed distinct transcriptional profiles.
• PV areas were enriched in fibro-inflammatory and vascular remodeling pathways.
• AD areas were enriched in lipid metabolism and antioxidant pathways.
• Cellular deconvolution revealed area- and disease-specific cell compositions.
• Ob-DM exhibited post-transcriptional modifications, including RNA editing and isoform switching in metabolic genes.

Conclusions:

• SLACS is technically feasible for spatial transcriptomic profiling of human VAT.
• Exploratory findings highlight distinct molecular signatures in VAT areas.
• Further validation in larger cohorts is warranted to confirm biological insights into adipose dysfunction.