Biology subjects

Bertrand, C.

Publications and source records attributed to Bertrand, C..

6 recordsLinked to original sources

bioRxiv2026

A cryptic hybrid zone reveals the genomic basis of flower colour variation in a plant with a large and complex genome

Flower colour is known to be a classic magic trait, undergoing divergent selection pressures exerted by distinct pollinators and involved in reproductive isolation. However, variation at this trait may also results from other eco-evolutionary factors whose interpretation requires throughout context-specific analyses. Here, we investigated the eco-evolutionary causes of pink- and yellow-flowered morphs in Pedicularis comosa where their parapatric ranges form a contact zone in the East of the Pyrenees Mountains. First, we generated a near-chromosome-scale reference genome assembly for this species. We then used a Genotyping By Sequencing approach to infer patterns of genetic diversity and differentiation between populations and morphs at a total of 158 individuals from 11 localities. We found that neutral genetic structure is primarily consistent with geography rather than with colour. However, admixture analyses and clines suggest the existence of a cryptic hybrid zone between morphs. Outlier detection methods and examination of locus-by-locus cline features, then allowed to pinpoint candidate loci to explain colour variation. To gain insight into the functional aspects of these loci, we finally analysed floral transcriptomes and quantified pigments using Liquid Chromatography coupled with Mass Spectrometry (LC-MS) and confirmed the involvement of key genes in the anthocyanin metabolic pathway (e.g. DFR, FLS) and associated pigments (e.g. cyanidin and delphinidin). Our results show that implementing a highly integrative multi-omic approach can allow unraveling the genetic basis and the eco-evolutionary significance of adaptive traits with even very limited previous knowledge, on species with large and complex genomes.

evolutionary biology↗

bioRxiv2024

Vascular damage and excessive proliferation compromise liver function after extended hepatectomy in mice

Surgical resection remains the gold standard for liver tumor treatment, yet the emergence of post-operative liver failure, known as the small for size syndrome (SFSS), poses a substantial challenge. The activation of hypoxia sensors in a SFSS liver remnant initiated early angiogenesis, improving vascular architecture, safeguarding against liver failure and reducing mortality. The study aimed to elucidate vascular remodeling mechanisms in SFSS, its impact on hepatocyte function and subsequent liver failure. Mice underwent extended partial hepatectomy to induce SFSS, a subset were exposed to hypoxia immediately after surgery. Hypoxia bolstered post- hepatectomy survival rates. Early proliferation of liver sinusoidal cells coupled with augmented recruitment of endothelial progenitor cells (EPC) via the VEGF/SDF-1 pathway resulted in heightened vascular density, improved lobular perfusion, and limited hemorrhagic events in the regenerating liver under hypoxia. The administration of G-CSF mimicked the effects of hypoxia on vascular remodeling and EPC recruitment, though it failed to rescue survival. Compared to normoxia, hypoxia restrained hepatocyte proliferation yet improved the function of the regenerating remnant, favoring functional preservation in the liver remnant. Injection of AAV8- TBG-HNF4 virus for hepatocyte-specific overexpression of HNF4, the master regulator of hepatocyte function, enforced functionality in proliferating hepatocytes. The combination, only, of HNF4 overexpression and G-CSF treatment rescued survival post-SFSS-setting hepatectomy. In summary, SFSS arises due to imbalance and desynchronized interplay between functional regeneration and vascular restructuring. To enhance survival following SFSS-hepatectomy, a two- pronged strategy is essential, addressing the preservation of function in the proliferating parenchymal cells alongside the simultaneous mitigation of vascular harm. One Sentence SummaryCombined treatment with G-CSF and HNF4 overexpression rescues vascular damage and function to improve survival after extended hepatectomy in mice.

cell biology↗

bioRxiv2023

Correction of non-random mutational biases along a linear bacterial chromosome by the mismatch repair endonuclease NucS

The linear chromosome of Streptomyces exhibits a highly compartmentalized structure with a conserved central region flanked by variable arms. As double strand break (DSB) repair mechanisms play a crucial role in shaping the genome plasticity of Streptomyces, we investigated the role of EndoMS/NucS, a recently characterized endonuclease involved in a non-canonical Mismatch Repair (MMR) mechanism in archaea and actinobacteria, that singularly corrects mismatches by creating a DSB. We showed that Streptomyces mutants lacking NucS display a marked colonial phenotype and a drastic increase in spontaneous mutation rate. In vitro biochemical assays revealed that NucS cooperates with the replication clamp to efficiently cleave G/T, G/G and T/T mismatched DNA by producing DSBs. These findings are consistent with the transition-shifted mutational spectrum observed in the mutant strains and reveal that NucS-dependent MMR specific task is to eliminate G/T mismatches generated by the DNA polymerase during replication. Interestingly, our data unveil a crescent-shaped distribution of the transition frequency from the replication origin towards the chromosomal ends, shedding light on a possible link between NucS-mediated DSBs and Streptomyces genome evolution. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/572499v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1aa491dorg.highwire.dtl.DTLVardef@a62657org.highwire.dtl.DTLVardef@1f1d2aorg.highwire.dtl.DTLVardef@b3b389_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2019

HOTAIR promotes an epithelial-to-mesenchymal transition through relocation of the histone demethylase Lsd1

Epithelial-to-mesenchymal transition (EMT) drives a loss of epithelial traits by neoplastic cells enabling metastasis and recurrence in cancer. HOTAIR emerged as one of the most renowned long noncoding RNAs promoting EMT mostly as a scaffold for PRC2 and repressive histone H3 Lys27 methylation at gene promoters. In addition to PRC2, HOTAIR interacts with the Lsd1 lysine demethylase, a known epigenetic regulator of cell fate during development and differentiation. However, Lsd1 role in HOTAIR function is still poorly understood. Here, through expression of truncated variants of HOTAIR, we revealed that, in contrast to PRC2, its Lsd1-interacting domain is essential for acquisition of migratory properties by epithelial cells. HOTAIR induces Lsd1 relocation from its inherent genomic loci hence reprogramming the epithelial transcriptome. Our results uncovered an unexpected role of HOTAIR in EMT as an Lsd1 effector and pointed to the importance of Lsd1 as a guardian of the epithelial identity.

cancer biology↗

bioRxiv2019

Galton-Watson Process And Bayesian Inference: A Turnkey Method For The Viability Study Of Small Populations

O_LISharp prediction of extinction times is needed in biodiversity monitoring and conservation management. C_LIO_LIThe Galton-Watson process is a classical stochastic model for describing population dynamics. Its evolution is like the matrix population model where offspring numbers are random. Extinction probability, extinction time, abundance are well known and given by explicit formulas. In contrast with the deterministic model, it can be applied to small populations. C_LIO_LIParameters of this model can be estimated through the Bayesian inference framework. This enables to consider nonarbitrary scenarios. C_LIO_LIWe show how coupling Bayesian inference with the Galton-Watson model provides several features: i) a flexible modelling approach with easily understandable parameters ii) compatibility with the classical matrix population model (Leslie type model) iii) A non-computational approach which then leads to more information with less computing iv) a non-arbitrary choice for scenarios, parameters... It can be seen to go one step further than the classical matrix population model for the viability problem. C_LIO_LITo illustrate these features, we provide analysis details for two examples whose one of which is a real life example. C_LI

ecology↗

bioRxiv2018

Different SUMO Paralogs Determine the Fate of WT and Mutant CFTRs: Biogenesis vs. Degradation

A pathway for CFTR degradation is initiated by Hsp27 which cooperates with Ubc9 and binds to the common F508del mutant to modify it with SUMO-2/3. These SUMO paralogs form poly-chains, which are recognized by the ubiquitin ligase, RNF4, for proteosomal degradation. Here, protein array analysis identified the SUMO E3, PIAS4, which increased WT and F508del CFTR biogenesis in CFBE airway cells. PIAS4 increased immature CFTR three-fold and doubled expression of mature CFTR, detected by biochemical and functional assays. In cycloheximide chase assays, PIAS4 slowed immature F508del degradation 3-fold and stabilized mature WT CFTR at the PM. PIAS4 knockdown reduced WT and F508del CFTR expression by 40-50%, suggesting a physiological role in CFTR biogenesis. PIAS4 modified F508del CFTR with SUMO-1 in vivo and reduced its conjugation to SUMO-2/3. These SUMO paralog specific effects of PIAS4 were reproduced in vitro using purified F508del NBD1 and SUMOylation reaction components. PIAS4 reduced endogenous ubiquitin conjugation to F508del CFTR by ~50%, and blocked the impact of RNF4 on mutant CFTR disposal. These findings indicate that different SUMO paralogs determine the fates of WT and mutant CFTRs, and they suggest that a paralog switch during biogenesis can direct these proteins to different outcomes: biogenesis vs. degradation.

cell biology↗