Chromatin architecture in laminopathies: a tale of LADs

  • Project leader:Philippe Collas
  • Info:Mutations in the lamin A (LMNA) gene, encoding lamin A/C, cause laminopathies, including familial partial lipodystrophies of type 2 (FPLD2). Partial lipodystrophies affect adipose tissue in a depot-specific manner and leads to insulin resistance, type-2 diabetes and other metabolic complications. Using patient-derived cells and engineered adipose stem cells expressing LMNA mutants, we investigate how FPLD2-causing LMNA mutations deregulate adipose progenitor cell nuclear envelope integrity, chromatin architecture and function. We combine cell biology, microscopy, proteomics and genomics approaches. Other mutations in the LMNA gene cause muscle dystrophies. We also explore how such mutations affect chromatin organization in cell models of myogenic differentiation (collaboration with Gisele Bonne, Paris).

Project participants

Julia Madsen-Østerbye, Kristin Vekterud, Nolwenn Briand, Louise Petersen, Anita Sørensen; collaborations with Coen Campsteijn, University of Oslo, Corinne Vigouroux, INSERM & Université Pierre et Marie Curie, Paris, Gisèle Bonne, INSERM and Hôpital Pitié-Salpétrière. Paris.

Ongoing research

  • Impact of the FPLD2-causing lamin A p.R482W mutation on functional nuclear and chromatin architecture during adipogenesis and in adipocytes
  • Impact of the lamin A p.R482W mutation on nuclear envelope integrity
  • De-regulation of chromatin at the nuclear periphery caused by lamin A mutations causing lipodystrophies and muscle dystrophies (collaboration with Gisèle Bonne)

Recent achievements