Nolwenn Briand
Nuclear architecture in lipodystrophic laminopathies
Mutations in the lamin A (LMNA) gene encoding lamin A/C cause laminopathies, including familial partial lipodystrophy of Dunnigan type 2 (FPLD2). FPLD2 affects adipose tissue in a depot-specific manner, leading to metabolic diseases. Some of these mutations affect the adipogenic potential of progenitor cells, as well as endothelial cell function, the latter being related to atherosclerosis, often detected in FPLD2 patients. Using patient-derived cells and engineered adipose progenitors, we investigate how lipodystrophic lamin A mutations deregulate adipose depot-specific progenitor cell nuclear architecture and function. We combine cell biology and high-throughput genomics approaches.
Epigenetic encoding of the thermogenic capacity of human adipose tissue
Adipose tissue has become a major research focus because of its capacity to store energy in the form of lipids in white adipocytes, and dissipate energy by heat in brown and beige – thermogenic – adipocytes. Worldwide, over 2 billion adults are overweight, including 1 billion clinically obese . The beneficial effect of thermogenic adipocytes in maintaining body weightand protecting against metabolic disorders has therefore raised strong interest in understanding their developmental origins and mechanisms of activation in response to environmental stimuli such as exposure to cold. In this project, we investigate the transcriptional and 3D epigenetic features of human beige adipocytes, that can convert between a whitened phenotype and a thermogenic beige phenotype in response to cold (β-adrenergic) stimuli (beiging). We combine cell biology, single-cell transcriptomics, epigenomics and 3D chromatin conformation studies to explore the epigenetic encoding and the 3D chromatin architecture directing this plasticity. 
Publications
Briand N, Collas P (2020). Lamina-associated domains: peripheral matters and internal affairs. Genome Biol 21(1):85.
Briand N, Guénantin AC, Jeziorowska D, Shah A, Mantecon M, Capel E, Garcia M, Oldenburg A, Paulsen J, Hulot JS, Vigouroux C, Collas P (2018). The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks. Hum Mol Genet 27(8):1447-1459.
Oldenburg AR, Briand N, Sørensen AL, Cahyani I, Shah A, Moskaug JØ, Collas P (2017). A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus. J Cell Biol 216(9):2731-2743.
Guénantin AC, Briand N, Capel E, Dumont F, Morichon R, Provost C, Stillitano F, Jeziorowska D, Siffroi JP, Hajjar RJ, Fève B, Hulot JS, Collas P, Capeau J, Vigouroux C (2017). Functional human beige adipocytes from induced pluripotent stem cells. Diabetes 66(6):1470-1478.
Paulsen J, Sekelja M, Oldenburg AR, Barateau A, Briand N, Delbarre E, Shah, A, Sørensen AL, Vigouroux C, Biendia B, Collas P (2017). Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts. Genome Biol 18(1):21.
Vadrot N, Duband-Goulet I, Cabet E, Attanda W, Barateau A, Vicart P, Gerbal F, Briand N, Vigouroux C, Oldenburg AR, Lund EG, Collas P, Buendia B (2015). The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 24(7):2069-20109.
Briand N, Prado C, Mabilleau G, Lasnier F, Le Lièpvre X, Covington JD, Ravussin E, Le Lay S, Dugail I (2014). Caveolin-1 expression and cavin stability regulate caveolae dynamics in adipocyte lipid store fluctuation. Diabetes 63(12):4032-44.
Briand N, Le Lay S, Sessa WC, Ferré P, Dugail I (2011). Distinct roles of endothelial and adipocyte caveolin-1 in macrophage infiltration and adipose tissue metabolic activity. Diabetes 60(2):448-53.
Le Lay S, Briand N, Blouin CM, Chateau D, Prado C, Lasnier F, Le Liepvre X, Hajduch E, Dugail I (2010). The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes. Autophagy 6(6):754-63.
Briand N, Dugail I, Le Lay S. 2011. Cavin proteins: New players in the caveolae field. Biochimie 93(1):71-7.
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Briand, Nolwenn & Collas, Philippe (2020). Lamina-associated domains: Peripheral matters and internal affairs. Genome Biology. ISSN 1465-6906. 21:85, p. 1–25. doi: 10.1186/s13059-020-02003-5. Full text in Research Archive
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Briand, Nolwenn; Cahyani, Inswasti; Madsen-Østerbye, Julia-Kristina Jensen; Paulsen, Jonas; Rønningen, Torunn & Sørensen, Anita Løvstad [Show all 7 contributors for this article] (2018). Lamin A, Chromatin and FPLD2:Not ust a Peripheral Ménage-à-Trois. Frontiers in Cell and Developmental Biology. ISSN 2296-634X. 6. doi: 10.3389/fcell.2018.00073. Full text in Research Archive
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Briand, Nolwenn; Guénantin, Anne-Claire; Jeziorowska, Dorota; Shah, Akshay; Mantecon, Matthieu & Capel, Emilie [Show all 12 contributors for this article] (2018). The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks. Human Molecular Genetics. ISSN 0964-6906. 27(8), p. 1447–1459. doi: 10.1093/hmg/ddy055.
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Briand, Nolwenn & Collas, Philippe (2018). Laminopathy-causing lamin A mutations reconfigure lamina-associated domains and local spatial chromatin conformation. Nucleus. ISSN 1949-1034. 9(1), p. 216–226. doi: 10.1080/19491034.2018.1449498. Full text in Research Archive
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Oldenburg, Anja; Briand, Nolwenn; Sørensen, Anita Løvstad; Cahyani, Inswasti; Shah, Akshay & Moskaug, Jan Øivind [Show all 7 contributors for this article] (2017). A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus. Journal of Cell Biology. ISSN 0021-9525. 216(9), p. 2731–2743. doi: 10.1083/jcb.201701043.
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Guénantin, Anne-Claire; Briand, Nolwenn; Capel, Emilie; Dumont, Florent; Morichon, Romain & Provost, Claire [Show all 15 contributors for this article] (2017). Functional human beige adipocytes from induced pluripotent stem cells. Diabetes. ISSN 0012-1797. 66(6), p. 1470–1478. doi: 10.2337/db16-1107.
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Paulsen, Jonas; Sekelja, Monika; Oldenburg, Anja; Barateau, Alice; Briand, Nolwenn & Delbarre, Erwan [Show all 11 contributors for this article] (2017). Chrom3D: Three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts. Genome Biology. ISSN 1465-6906. 18:21, p. 1–15. doi: 10.1186/s13059-016-1146-2.
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Vadrot, Nathalie; Duband-Goulet, Isabelle; Cabet, Eva; Attanda, Wikayatou; Barateau, Alice & Vicart, Patrick [Show all 13 contributors for this article] (2014). The p.R482W substitution in a-type lamins deregulates SREBP1 activity in dunnigan-type familial partial lipodystrophy. Human Molecular Genetics. ISSN 0964-6906. 24(7), p. 2096–2109. doi: 10.1093/hmg/ddu728.
