About our research
The 3-dimensional layout of chromatin, including interactions with the nuclear envelope at the nuclear periphery, plays important roles in the establishment of gene expression programs that govern cell fate decisions. In white adipose tissue, a population of adipocyte progenitors differentiate into white adipocytes, which store lipids; another also gives rise to thermogenic 'beige' adipocytes. We are addressing the following questions:
- How do chromatin states and 3D conformation regulate adipose stem cell differentiation and adipocyte function?
- How do lamin A mutations causing partial lipodystrophies (FLPD2) affect nuclear architecture and differentiation?
- How do cells maintain chromatin integrity in normal and pathological contexts?
- How are nuclear envelope - chromatin interactions regulated?
Our work combines molecular, genomics, microscopy imaging and computational approaches using normal and cancer cells, patient cells and engineered mesenchymal stem cells from adipose tissue.
Our lab’s research history in brief
- dynamics of the nuclear envelope during differentiation
- lamina-associated domains (LADs) during the circadian cycle (Brunet 2019 Front Genet)
- 3D changes in genome conformation during adipogenic differentiation: TAD cliques (Paulsen 2019 Nature Genet)
- FLPD2-causing lamin A mutation and adipogenic deregulation ( Briand 2018 Hum Mol Genet; Oldenburg 2017 J Cell Biol; Oldenburg 2014 Hum Mol Genet)
- 3D genome modeling (Paulsen 2017 Genome Biol; Paulsen 2018 Nature Protoc); Chrom3D package on github: https://github.com/Chrom3D/Chrom3D
- nuclear lamina-chromatin interactions during adipogenic differentiation, (Lund 2013 Genome Res; Lund 2015 Nucl Acids Res; Rønningen 2015 Genome Res); EDD package on github: https://github.com/CollasLab/edd
- deposition of histone variant H3.3 into chromatin (Delbarre 2010 Mol Biol Cell; Delbarre 2013 Genome Res; Ivanauskiene 2014 Genome Res: Delbarre 2017 Genome Res)
- epigenetic patterning of developmental gene expression (Lindeman 2011 Dev Cell; Andersen 2012 Genome Biol) and adipocyte differentiation (Boquest 2007 Stem Cells; Sørensen 2010 Mol Biol Cell; Shah 2014 BMC Genomics; Rønningen 2015 Genome Res)
- chromatin immunoprecipitation (ChIP) for small cell numbers (Dahl 2008 Nature Protoc; Dahl 2009 Genome Biol)
- cell and nuclear reprogramming (Håkelien 2002 Nature Biotech; Taranger 2005 Mol Biol Cell; Freberg 2007 Mol Biol Cell)
- disassembly and reformation of the nuclear envelope (Steen 2000 J Cell Biol; Steen 2001 J Cell Biol; Martins 2003 J Cell Biol)