Unique Adipose Stem Cell Traits Shape Fat Depot Features
Summary
In mammalian species, white adipose tissues predominantly bifurcate into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT), each possessing distinct metabolic attributes. While burgeoning evidence intimates that adipose stem cell (ASC) subpopulations may elucidate fat depot disparities, a comparative examination of ASCs from both depots remains absent. In this study, researchers characterized heterogeneous ASCs and scrutinized the impact of intrinsic and tissue micro-environmental determinants on disparate ASC features. They substantiated that ASC subpopulations within EAT and IAT manifested divergent molecular characteristics spanning three adipogenic phases. ASC transplantation investigations disclosed that intrinsic ASC properties chiefly dictated adipogenic potential. Under obesogenic provocation, EAT-specific SDC1+ ASCs facilitated fibrotic remodeling, while IAT-specific CXCL14+ ASCs mitigated macrophage infiltration. Additionally, IAT-specific BST2high ASCs displayed a pronounced propensity to differentiate into beige adipocytes. In aggregate, their findings expound upon ASC understanding and proffer novel perspectives on the genesis of white fat depot variation.
Fig.1 Graphical abstract. (Nahmgoong, 2022)
Research Criteria
The authors used single-cell RNA-seq to characterize heterogeneous adipose stem cell subpopulations from normal and obese mice. They showed that fat depot-specific adipose stem cell subpopulations, such as WNT2+, SDC1+, CXCL14+, and BST2high cells, are crucial for distinct metabolic features of visceral and subcutaneous white fat depots.
Sample Type
Result—In EAT and IAT, ASC Clusters Exhibit Different Molecular Properties and Comprise Three Adipogenic Stages
Employing unsupervised clustering analysis on 11,225 quality control-validated cells divulged that ASCs from NCD mice bifurcated into four ASC clusters within EAT and seven ASC clusters in IAT. The molecular characteristics of ASC clusters in EAT and IAT likely diverged, partly attributable to fat depot-specific genes in IAT. Given the heterogeneous nature of ASCs and their variable adipogenic potentials, ASC cluster differentiation trajectories were inferred utilizing Palantir. Analogously, IAT ASC clusters coalesced into three stages: IS1, IS2, and IS3. To substantiate the adipogenic hierarchy of ASC stages, FACS was employed to isolate and characterize ASCs in EAT and IAT. DPP4 and ICAM1 emerged as appropriate markers for isolating S1, S2, and S3 ASCs. Cultured ES2 and ES3 ASCs demonstrated augmented lipid droplet formation and adipocyte marker gene expression compared to ES1 ASCs, whereas ES1 ASCs exhibited enhanced cell proliferation and osteogenic potential. Similarly, IS1, IS2, and IS3 ASCs manifested disparate adipogenic and osteogenic potentials. Nevertheless, gene expression profiles of EAT and IAT ASCs across adipogenic stages evinced marked differences, insinuating distinct biological features among subpopulations.
Fig.2 In EAT and IAT, ASC clusters exhibit different molecular properties and comprise three adipogenic stages. (Nahmgoong, 2022)
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Reference
- Nahmgoong, H.; et al. Nahmgoong, Hahn, et al. "Distinct properties of adipose stem cell subpopulations determine fat depot-specific characteristics. Cell Metabolism. 2022, 34(3): 458-472.
