What question did this study set out to answer?

To evaluate how single-cell multi-omics technologies characterize cellular heterogeneity, lineage trajectories, and pathological states in human adipose tissue.

September 27, 2024Stem Cell Research & Therapy12 citationsOpen Access

Dissecting human adipose tissue heterogeneity using single‐cell omics technologies

GRGiuliana Di RoccoCellular Therapeutics (United Kingdom)ATAngelo TrivisonnoLibera Università Maria SS. Assunta GTGiovanni TrivisonnoUniversità Campus Bio-Medico

Puntos clave

To evaluate how single-cell multi-omics technologies characterize cellular heterogeneity, lineage trajectories, and pathological states in human adipose tissue.
Synthesized findings across single-cell genomic, epigenomic, transcriptomic, proteomic, lipidomic, and matrisomic platforms applied to adipose biology.
Assessed technical variability, biological heterogeneity, and tissue harvesting methods affecting subcutaneous adipose tissue translational quality standards.
Single-cell technologies resolve rare progenitor subpopulations, lineage hierarchies, and altered immunomodulatory profiles within adipose tissue depots.
High-resolution profiling links distinct dysfunctional adipocyte states to the progression of obesity, type 2 diabetes, and cancer microenvironment remodeling.
Molecular mapping provides definitive cellular benchmarks essential for standardizing cell-based and cell-free regenerative therapies.

Resumen

Single-cell omics technologies that profile genes (genomic and epigenomic) and determine the abundance of mRNA (transcriptomic), protein (proteomic and secretomic), lipids (lipidomic), and extracellular matrix (matrisomic) support the dissection of adipose tissue heterogeneity at unprecedented resolution in a temporally and spatially defined manner. In particular, cell omics technologies may provide innovative biomarkers for the identification of rare specific progenitor cell subpopulations, assess transcriptional and proteomic changes affecting cell proliferation and immunomodulatory potential, and accurately define the lineage hierarchy and differentiation status of progenitor cells. Unraveling adipose tissue complexity may also provide for the precise assessment of a dysfunctional state, which has been associated with cancer, as cancer-associated adipocytes play an important role in shaping the tumor microenvironment supporting tumor progression and metastasis, obesity, metabolic syndrome, and type 2 diabetes mellitus. The information collected by single-cell omics has relevant implications for regenerative medicine because adipose tissue is an accessible source of multipotent cells; alternative cell-free approaches, including the use of adipose tissue stromal cell-conditioned medium, extracellular vesicles, or decellularized extracellular matrix, are clinically valid options. Subcutaneous white adipose tissue, which is generally harvested via liposuction, is highly heterogeneous because of intrinsic biological variability and extrinsic inconsistencies in the harvesting and processing procedures. The current limited understanding of adipose tissue heterogeneity impinges on the definition of quality standards appropriate for clinical translation, which requires consistency and uniformity of the administered product. We review the methods used for dissecting adipose tissue heterogeneity and provide an overview of advances in omics technology that may contribute to the exploration of heterogeneity and dynamics of adipose tissue at the single-cell level.

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