Aurelie Nathalie Pascale Bellanger

• Potolitsyna, Evdokiia; Pickering, Sarah Jai Hazell; Bellanger, Aurelie Nathalie Pascale; Germier, Thomas Lodewijk Guy; Collas, Philippe & Briand, Nolwenn (2024). Cytoskeletal rearrangement precedes nucleolar remodeling during adipogenesis. Communications Biology. 7. doi: 10.1038/s42003-024-06153-1. Full text in Research Archive Show summary

  Differentiation of adipose progenitor cells into mature adipocytes entails a dramatic reorganization of the cellular architecture to accommodate lipid storage into cytoplasmic lipid droplets. Lipid droplets occupy most of the adipocyte volume, compressing the nucleus beneath the plasma membrane. How this cellular remodeling affects sub-nuclear structure, including size and number of nucleoli, remains unclear. We describe the morphological remodeling of the nucleus and the nucleolus during in vitro adipogenic differentiation of primary human adipose stem cells. We find that cell cycle arrest elicits a remodeling of nucleolar structure which correlates with a decrease in protein synthesis. Strikingly, triggering cytoskeletal rearrangements mimics the nucleolar remodeling observed during adipogenesis. Our results point to nucleolar remodeling as an active, mechano-regulated mechanism during adipogenic differentiation and demonstrate a key role of the actin cytoskeleton in defining nuclear and nucleolar architecture in differentiating human adipose stem cells.

• Rossini, Roberto; Oshaghi, Mohammadsaleh; Nekrasov, Maxim; Bellanger, Aurelie Nathalie Pascale; Domaschenz, Renae & Dijkwel, Yasmin [Show all 10 contributors for this article] (2023). Multi-level 3D genome organization deteriorates during breast cancer progression. BioRxiv. ISSN 0362-4331. doi: 10.1101/2023.11.26.568711. Full text in Research Archive
• Bellanger, Aurelie Nathalie Pascale; Madsen-Østerbye, Julia-Kristina; Galigniana, Natalia & Collas, Philippe (2022). Restructuring of Lamina-Associated Domains in Senescence and Cancer. Cells. 11(11). doi: 10.3390/cells11111846. Full text in Research Archive Show summary

  Induction of cellular senescence or cancer is associated with a reshaping of the nuclear envelope and a broad reorganization of heterochromatin. At the periphery of mammalian nuclei, heterochromatin is stabilized at the nuclear lamina via lamina-associated domains (LADs). Alterations in the composition of the nuclear lamina during senescence lead to a loss of peripheral heterochromatin, repositioning of LADs, and changes in epigenetic states of LADs. Cancer initiation and progression are also accompanied by a massive reprogramming of the epigenome, particularly in domains coinciding with LADs. Here, we review recent knowledge on alterations in chromatin organization and in the epigenome that affect LADs and related genomic domains in senescence and cancer.

• Madsen-Østerbye, Julia-Kristina; Bellanger, Aurelie Nathalie Pascale; Galigniana, Natalia & Collas, Philippe (2022). Biology and Model Predictions of the Dynamics and Heterogeneity of Chromatin-Nuclear Lamina Interactions. Frontiers in Cell and Developmental Biology. 10, p. 1–13. doi: 10.3389/fcell.2022.913458. Full text in Research Archive Show summary

  Associations of chromatin with the nuclear lamina, at the nuclear periphery, help shape the genome in 3 dimensions. The genomic landscape of lamina-associated domains (LADs) is well characterized, but much remains unknown on the physical and mechanistic properties of chromatin conformation at the nuclear lamina. Computational models of chromatin folding at, and interactions with, a surface representing the nuclear lamina are emerging in attempts to characterize these properties and predict chromatin behavior at the lamina in health and disease. Here, we highlight the heterogeneous nature of the nuclear lamina and LADs, outline the main 3-dimensional chromatin structural modeling methods, review applications of modeling chromatin-lamina interactions and discuss biological insights inferred from these models in normal and disease states. Lastly, we address perspectives on future developments in modeling chromatin interactions with the nuclear lamina.

• Vietri, Marina; Schultz, Sebastian; Bellanger, Aurélie Nathalie Pascale; Jones, Carl; Petersen, Louise I & Raiborg, Camilla [Show all 20 contributors for this article] (2020). Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmention. Nature Cell Biology. ISSN 1465-7392. 22, p. 856–867. doi: 10.1038/s41556-020-0537-5. Full text in Research Archive Show summary

  The ESCRT-III membrane fission machinery maintains the integrity of the nuclear envelope. Although primary nuclei resealing takes minutes, micronuclear envelope ruptures seem to be irreversible. Instead, micronuclear ruptures result in catastrophic membrane collapse and are associated with chromosome fragmentation and chromothripsis, complex chromosome rearrangements thought to be a major driving force in cancer development. Here we use a combination of live microscopy and electron tomography, as well as computer simulations, to uncover the mechanism underlying micronuclear collapse. We show that, due to their small size, micronuclei inherently lack the capacity of primary nuclei to restrict the accumulation of CHMP7–LEMD2, a compartmentalization sensor that detects loss of nuclear integrity. This causes unrestrained ESCRT-III accumulation, which drives extensive membrane deformation, DNA damage and chromosome fragmentation. Thus, the nuclear-integrity surveillance machinery is a double-edged sword, as its sensitivity ensures rapid repair at primary nuclei while causing unrestrained activity at ruptured micronuclei, with catastrophic consequences for genome stability.

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