Biology subjects

Durand, J.

Publications and source records attributed to Durand, J..

6 recordsLinked to original sources

bioRxiv2026

KDM6B interacts with nucleo-adhesome components CSRP2 and TGFB1I1 to regulate EMT

The methyltransferase EZH2 (Enhancer of Zest Homolog 2) and the demethylase KDM6B (Lysine Demethylase 6B) have been associated with epithelial to mesenchymal transition (EMT) and poor prognosis in various cancers. These enzymes methylate and demethylate H3K27me3 and regulate distinct sets of genes controlling EMT induction, despite having opposite catalytic activities. This could be due to their recruitment or the modulation of their activity by partner proteins on specific loci. This work sought to identify proteins associated with chromatin and interacting with EZH2 or with KDM6B during EMT. To do so, co-immunoprecipitation and mass spectroscopy was used under TGF{beta} (Tumor growth factor {beta}) and TNF (Tumor necrosis factor ) treatment to induce EMT in A549 lung cancer cells. Surprisingly, numerous proteins related to focal adhesions were identified to interact with EZH2 or KDM6B. These proteins are part of a nuclear protein interaction network previously described as nucleo-adhesome. Among these proteins, TGFB1I1 (transforming growth factor induced peptide 1) and CSRP2 (cysteine and glycine rich protein 2) were further confirmed to interact with KDM6B in the nucleus and even more so during EMT. The target genes of these complexes were then sought by knocking down KDM6B, TGFB1I1 or CSRP2. Three genes (coding Integrin alpha 5, Laminin y2 and Matrix Metalloproteinase 9) were confirmed to be regulated by KDM6B, TGFB1I1 and CSRP2. These findings may have clinical relevance, as immunohistochemistry analyses performed on a cohort of lung cancer patients revealed increased nuclear localization of TGFB1I1 and CSRP2 in cells undergoing EMT.

cell biology↗

bioRxiv2026

Neocortical astrocyte diversity stems from distinct developmental origins

Key regulators of neural network activity in multiple advanced cognitive processes and essential components of the blood-brain barrier, astrocytes constitute a highly heterogeneous population at the morphological, molecular, and functional levels. However, how this diversity arises during mammalian brain development remains poorly investigated. Here, using a combination of multicolour genetic fate mapping, single-cell transcriptomic analyses, multichannel large-volume imaging and detailed 3D cell morphology reconstructions, we uncover a discrete subpopulation of neocortical astrocytes generated from an early restricted embryonic domain located outside of the dorsal pallium. Besides their separate lineage from pyramidal neurons, these astrocytes exhibit a developmental trajectory that differs from astrocytes produced by dorsal cortical progenitors, including different migratory pathways, spatial distributions and morphology. Overall, our results reveal the diversity of embryonic sources responsible for neocortical astrocyte genesis and provide key insights into the unsuspected complex developmental processes that underlie cortical astrocyte heterogeneity.

neuroscience↗

bioRxiv2026

Long-projection astrocytes challenge canonical territorial organization in the sleep-promoting VLPO

The ventrolateral preoptic nucleus (VLPO) is a key hypothalamic hub for non-rapid eye movement sleep, yet the glial architecture supporting its circuits remains poorly understood. Here, combining genetic labeling, high-resolution imaging and calcium imaging, we uncover unexpected astrocyte diversity in the VLPO. In addition to classical protoplasmic astrocytes, we identify paired "doublet" astrocytes associated with high local proliferative activity, as revealed by EdU incorporation. We further describe a population of long-projection astrocytes extending processes far beyond canonical astrocytic territories and contacting distant cells. These projections challenge the classical territorial organization of astrocytes and resemble morphologies previously thought to be restricted to hominid brains. Notably, VLPO astrocytes display robust spontaneous Ca{superscript 2} activity and a highly functionally connected network compared to astrocytes in the cortex and hippocampus. Together, these findings reveal specialized astrocyte architectures and enhanced glial network integration within a sleep-promoting nucleus. Reporting summaryBellier et al. identify three astrocyte subtypes in the sleep-promoting VLPO, including long-projection astrocytes with hominid-like morphology. They uncover marked postnatal gliogenesis, distinctive spontaneous Ca{superscript 2} dynamics, and tightly interconnected astrocytic networks, revealing region-specific astrocyte specialization and enhanced glial communication.

neuroscience↗

bioRxiv2026

Metabolic engineering of Escherichia coli strains for the in vivo synthesis of GP-mediated oligosaccharides

Enzymatic synthesis of rare disaccharides by reverse-phosphorolysis is a potentially sustainable route to produce high-value glycosides for human health and nutrition. We report the metabolic engineering of Escherichia coli for in vivo production of {beta}-mannobiose with different osidic linkages from hexose sugars. We demonstrate production of {beta}-1,2-mannobiose with this approach as proof of concept. Phosphotransferase system (PTS) inactivation enables import of non-phosphorylated mannose via heterologous permease GalP, restoring growth on mannose in a PTS- background and allowing mannose into the reverse biosynthetic pathway. Deletion of pfkA, which promotes intracellular accumulation of key sugar phosphates (G1P, M1P), establishes a favorable metabolic chassis for oligosaccharide production using glycoside-phosphorylases. Using this chassis, we expressed two {beta}-mannoside phosphorylases to enable the direct production of {beta}-1,2- and {beta}-1,4-mannobiose from mannose. The same chassis was also employed for laminaribiose production through the expression of a laminaribiose-phosphorylase. pfkA deletion significantly increased product titer (> 0.6 g{middle dot}L-1) and yield (up to 9% g/g mannose), highlighting a favorable redistribution of carbon fluxes toward disaccharide formation. Moreover, a combination of mixed-substrate cultures using glycerol as carbon and energy source and further metabolic engineering enabled partial growth-production decoupling, redirecting mannose utilization primarily toward product synthesis, with a yield of 60%. These results demonstrate the modularity and efficiency of the proposed platform for fermentative production of non-conventional oligosaccharides and expand the scope of metabolic engineering strategies for glycoside biosynthesis.

synthetic biology↗

bioRxiv2024

Vascular dysfunction is at the onset of oxaliplatin-induced peripheral neuropathy symptoms in mice

Oxaliplatin-induced peripheral neuropathy (OIPN) is an adverse side effect of this chemotherapy used for gastrointestinal cancers. The continuous pain experienced by OIPN patients often result in the reduction or discontinuation of chemotherapy, thereby affecting patient survival. Several pathogenic mechanisms involving sensory neurons were shown to participate in the occurrence of OIPN symptoms. However, the dysfunction of the blood-nerve barrier as a source of nerve alteration had not been thoroughly explored. To characterise the vascular contribution to OIPN symptoms, we undertook two comparative transcriptomic analyses from mouse purified brain and sciatic nerve blood vessels (BVs), and nerve BVs after oxaliplatin or control administration. These analyses reveal distinct molecular landscapes between brain and nerve BVs and the upregulation of transcripts involved in vascular contraction after oxaliplatin treatment. Anatomical examination of the nerve yet shows the preservation of BV architecture in acute OIPN mouse model, although treated mice exhibit both neuropathic symptoms and enhanced vasoconstriction reflected by hypoxia. Moreover, vasodilators significantly reduce oxaliplatin-induced neuropathic symptoms and endoneurial hypoxia, establishing the key involvement of nerve blood flow in OIPN.

neuroscience↗

bioRxiv2023

Terrestrial Support of Aquatic Food Webs via an Overlooked Pathway-Inorganic Carbon and its Significance to Global Carbon Cycle

Freshwater ecosystems receive substantial terrestrial organic matter (t-OM) from surrounding landscapes. How the t-OM is transferred affects aquatic food webs and global carbon budgets. Previous studies have emphasized terrestrial support of aquatic ecosystems via direct organic carbon subsidy, overlooking the dissolved inorganic carbon (DIC) pathway, that is, DIC from t-OM decomposition is used by aquatic primary producers, supporting higher trophic levels. Using 2-year 13C and 15N measurements of phytoplankton, zooplankton, terrestrial plants, sediments, dissolved and particulate organic matter from seasonal wetlands, we found that while zooplankton (mid-trophic consumers) used t-OM directly in January, in March and May zooplankton were mainly supported by phytoplankton that used DIC recycled from t-OM mineralization and methanogenesis. The dominance of this DIC pathway is tightly coupled with the characteristics of these systems. Mineralization and methanogenesis of rich fresh t-OM resulted in supersaturated CO2 with high CO2 and CH4 emissions. Atmospheric CO2 diffusion and methanogenesis significantly enriched{delta} 13C of DIC, leading to wide variations in{delta} 13C of DIC between -12.4 and 6.7 {per thousand}, which provided ideal conditions to quantify carbon cycling in these widespread but understudied ecosystems. Our findings draw attention to potentially high carbon emissions from temporary freshwater ecosystems that are being increasingly common under warming climate.

ecology↗