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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Ferdinand Von Meyenn, Swiss Federal Institute of Technology Zurich, Switzerland
- Second opponent: Tenure-track lecturer Rubén Cereijo, University of Barcelona, Spain
- Third member and chair of the evaluation committee: Professor Yvonne Böttcher, University of Oslo
Chair of the Defence
Associate Professor Jean-Luc Boulland, University of Oslo
Principal Supervisor
Researcher, Nolwenn Briand, University of Oslo
Summary
Adipose tissue plasticity plays a critical role in maintaining metabolic homeostasis and represents an important focus of research in a world with a growing prevalence of obesity and type 2 diabetes. The presence of thermogenic beige adipocytes within white adipose tissue correlates with a lean, metabolically healthy phenotype in adults. Yet, the mechanisms underlying individual variations in thermogenic capacity remain poorly understood.
To understand the regulation of beige adipocyte identity and lineage specification, we investigated the transcriptome and 3D epigenome of human white and beige mature adipocytes and mapped early adipogenic differentiation at single-cell resolution. As a model, we differentiated primary adipose stem cells isolated from six unrelated individuals in the presence or absence of the beiging agent rosiglitazone, generating matched beige and white adipocytes.
We define a range of cell states among adipose progenitors during early white and beige adipogenesis, including several bipotential progenitor populations that can produce both white and beige adipocytes.
Further, we characterised the transcriptomic and epigenetic landscape of mature adipocytes and found that alternative isoform usage makes a significant contribution to the functional transcriptome of beige versus white adipocytes. We discovered a novel beige-specific isoform of PEMT and alternative TSS usage of key transcription factor PPARy.
In addition, we identified increased active epigenetic marks and enhancer contacts in beige adipocytes. White adipocytes, in comparison, have an enrichment for different epigenetic markers, highlighting distinctive features of the epigenome between beige and white adipocytes.
Together this thesis provides insights into the transcriptional heterogeneity of adipose progenitors, early adipogenesis and the epigenetic regulation of healthy white and beige cultured adipocytes.
Additional information
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