Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin
| Autor: | Mikael Rydén, Alma Andersson, Hui Gao, Lucas Massier, Jesper Bäckdahl, Jutta Jalkanen, Qian Li, Patrik L. Ståhl, Niklas Mejhert, Nayanika Bhalla, Anders Thorell, Lovisa Franzén |
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| Rok vydání: | 2021 |
| Předmět: |
Physiology
Insulin medicine.medical_treatment Adipose Tissue White Cell RNA Stimulation White adipose tissue Cell Biology Biology Cell biology chemistry.chemical_compound medicine.anatomical_structure chemistry Adipose Tissue Adipocyte medicine Adipocytes Humans Insulin Resistance Gene Molecular Biology Function (biology) |
| Zdroj: | Cell Metabolism |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2021.07.018 |
| Popis: | Summary The contribution of cellular heterogeneity and architecture to white adipose tissue (WAT) function is poorly understood. Herein, we combined spatially resolved transcriptional profiling with single-cell RNA sequencing and image analyses to map human WAT composition and structure. This identified 18 cell classes with unique propensities to form spatially organized homo- and heterotypic clusters. Of these, three constituted mature adipocytes that were similar in size, but distinct in their spatial arrangements and transcriptional profiles. Based on marker genes, we termed these AdipoLEP, AdipoPLIN, and AdipoSAA. We confirmed, in independent datasets, that their respective gene profiles associated differently with both adipocyte and whole-body insulin sensitivity. Corroborating our observations, insulin stimulation in vivo by hyperinsulinemic-euglycemic clamp showed that only AdipoPLIN displayed a transcriptional response to insulin. Altogether, by mining this multimodal resource we identify that human WAT is composed of three classes of mature adipocytes, only one of which is insulin responsive. |
| Databáze: | OpenAIRE |
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