We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Alternative isoform expression of key thermogenic genes in human beige adipocytes.
- Authors
Pickering, Sarah Hazell; Abdelhalim, Mohamed; Collas, Philippe; Briand, Nolwenn
- Abstract
Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes. Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing. Results: We find 777 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 562 genes. Importantly, only 10% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte differentiation. Functional classification of alternative isoforms points to a gain of function for key thermogenic transcription factors such as PPARG and CITED1, and enzymes such as PEMT, or LPIN1. We find that a large majority of the splice variants arise from differential TSS usage, with beige-specific TSSs being enriched for PPARg and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARg and PEMT. Discussion: These results suggest that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification.
- Subjects
GENE expression; ADIPOGENESIS; GENETIC regulation; RNA splicing; ALTERNATIVE RNA splicing; FAT cells; HUMAN genes
- Publication
Frontiers in Endocrinology, 2024, p1
- ISSN
1664-2392
- Publication type
Article
- DOI
10.3389/fendo.2024.1395750