Biology subjects

Marchal, P.

Publications and source records attributed to Marchal, P..

3 recordsLinked to original sources

bioRxiv2025

How Ikaros and Aiolos homo- and heterodimers drive gene expression to ensure B cell development

Ikaros family transcription factors (TF) are major regulators of cell differentiation and function. They function as homo- and heterodimers, but the contribution of specific dimers to gene regulation is unknown. We investigated the function of Ikaros-Ikaros, Ikaros-Aiolos and Aiolos-Aiolos in B cell development, and show that the dimers are not equivalent. Ikaros homodimers are required in proB and large preB cells where they bind and regulate the expression of a surprisingly small number of genes related to cell adhesion and migration, predominantly as transcriptional repressors. In contrast, Ikaros-Aiolos heterodimers and Aiolos homodimers are required in small preB and immature IgM+ B cells to regulate 10-fold larger target gene repertoires involved in B cell receptor signaling and immune functions. Aiolos-containing dimers act mainly as repressors in small preB cells but activators in immature B cells, where Aiolos-Aiolos antagonizes Ikaros-Ikaros. Mechanistically, Aiolos binds more GGAA motifs with different flanking nucleotides than Ikaros, which depends on a single amino acid difference in zinc finger 3 of its DNA binding domain. These results illustrate how homo- and heterodimerization of homologous TF proteins can markedly impact binding specificity, target gene response and pathway modulation in cells of the same lineage.

immunology↗

bioRxiv2024

MorphoCellSorter: An Andrews plot-based sorting approach to rank microglia according to their morphological features

Microglia exhibit diverse morphologies reflecting environmental conditions, maturity or functional states. Thus, morphological characterization provides important information to understand microglial roles and functions. Most recent morphological analysis relies on classifying cells based on morphological parameters. However, this classification may lack biological relevance, as microglial morphologies represent a continuum rather than distinct, separate groups, and do not correspond to mathematically defined, clusters irrelevant of microglial cells function. Instead, we propose a new open-source tool, MorphoCellSorter, which assesses microglial morphology by automatically computing morphological criteria, using principal component analysis and Andrews plots to rank cells. MorphoCellSorter properly ranked cells from various microglia datasets in mice and rats of different age, from in vivo, in vitro and ex vivo models, that were acquired using diverse imaging techniques. This approach allowed for the discrimination of cell populations in various pathophysiological conditions. Finally, MorphoCellSorter offers a versatile, easy and ready-to-use method to evaluate microglial morphological diversity that could easily be generalized to standardize practices across laboratories.

neuroscience↗

bioRxiv2023

Synaptic strength dynamics at cortical synaptic pathways is encoded by vigilance states duration

Interactions among brain areas are essential to most cognitive functions. Neuronal interactions between these areas depend on the modulation of synaptic strength. However, this modulation remains poorly understood. We recorded evoked synaptic responses at four hippocampal pathways in freely moving male rats across 24 hours: the Perforant Path to Dentate Gyrus (PP-DG), Fornix to Prefrontal Cortex (Fx-PFC), Fornix to Nucleus Accumbens (Fx-NAc), and the Schaffer Collaterals to CA1 (SC-CA1). We preserved the temporal dynamics of vigilance states and synaptic responses and show for the first time that synaptic strength at these four hippocampal pathways oscillates, with a very slow periodicity. We demonstrate that synaptic strength at the PP-DG, Fx-PFC, Fx-NAc pathways show a positive correlation with the duration of active wakefulness (aWK) and a negative one with the duration of most sleep states (slow wave sleep (SWS) and rapid eye movement sleep (REM)), with a positive peak correlation time-lag of 1 to 10 minutes for aWK and SWS at these 3 pathways. In contrast, no significant correlation peak is found at the SC-CA1 pathway. Finally, a model based on hypnogram data and synaptic strength at the PP-DG pathway was able to predict the evolution of synaptic strength at the PP-DG, Fx-PFC and Fx-NAc pathways, but not at the SC-CA1 pathway. These results reveal that the temporal succession of vigilance states, particularly aWK and SWS, may contribute to memory processes through rapid modulation of synaptic strength at several pathways during the sleep-wakefulness cycle, suggesting that memory processes are not only dependent on sleep amount but also on sleep architecture.

neuroscience↗