Regulation of adipocyte development and function by nuclear lamins and chromatin

  • Project leader:Nolwenn Briand (adipose biology), Philippe Collas (nuclear biology)
  • Info:Configuration of the genome and interactions of chromatin with the nuclear lamina are important regulators of differentiation of adipose progenitor cells into adipocytes. Mutations in A-type lamins cause familial partial lipodystrophy of Dunnigan type FPLD2 (among other laminopathies) and affect adipose tissue in a depot-specific manner, leading to metabolic diseases. Using patient-derived cells and engineered adipose progenitors, we investigate the mechanisms controlling white and thermogenic beige adipogenesis, and how lipodystrophic lamin A mutations deregulate adipose depot-specific progenitors.

Project participants

Julia Madsen-Østerbye, Natalia Galigniana, Mohamed Abdelhalim, Nolwenn Briand, Thomas Sæther, Evdokiia Potolitsyna, Anita Sørensen, Sarah Hazel Pickering, 

Image: Intracellular lipid (green), DNA (blue) and nucleolus (red) staining in an in vitro-differentiated human adipocyte (Nolwenn Briand & Evdokiia Potolitsyna)

Ongoing research

  • Chromatin-associated mechanisms of regulation of upper vs. lower body fat tissue expansion
  • Lamin-chromatin interactions and spatial chromatin organization during adipogenic differentiation towards white and beige lineages

Recent findings

  • Differential chromatin interactions with A- and B-type lamins (Forsberg 2019 Nucleus 10, 7-20)
  • Lipodystrophic lamin A mutation deregulates vascular differentiation gene networks (Briand, Guénantin 2018 Hum Mol Genet 27, 1447-1459)
  • Lipodystrophic lamin A mutation deregulates epigenetic and spatial conformation of anti-adipogenic MIR335 locus and adipose differentiation (Oldenburg 2014 Hum Mol Genet 23, 1151-1162; Oldenburg 2017 J Cell Biol  216, 2731-2743)
  • Lipodystrophic lamin A mutation alters radial positioning of loci (Paulsen 2017 Genome Biol 18, 21)
  • Association of lamin A with the genome during adipogenic differentiation (Rønningen 2015 Genome Res 25, 1825-1835;  Lund 2013 Genome Res 23, 1580-1589)