Biology subjects

Wenger, Y.

Publications and source records attributed to Wenger, Y..

4 recordsLinked to original sources

bioRxiv2020

Guidelines for accurate genotyping of SARS-CoV-2 using amplicon-based sequencing of clinical samples

BackgroundSARS-CoV-2 genotyping has been instrumental to monitor virus evolution and transmission during the pandemic. The reliability of the information extracted from the genotyping efforts depends on a number of aspects, including the quality of the input material, applied technology and potential laboratory-specific biases. These variables must be monitored to ensure genotype reliability. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in studies of viral spread and evolution. ResultsWe used clinical samples and synthetic viral genomes to evaluate the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination using an amplicon-based approach. We found that at least 1000 viral genomes are necessary to confidently detect variants in the genome at frequencies of 10% or higher. The broad applicability of our recommendations was validated in >200 clinical samples from six independent laboratories. The genotypes of clinical isolates with viral load above the recommended threshold cluster by sampling location and period. Our analysis also supports the rise in frequency of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was favoured by travelling during the summer 2020. ConclusionsWe present much-needed recommendations for reliable determination of SARS-CoV-2 genome sequence and demonstrate their broad applicability in a large cohort of clinical samples.

genomics↗

bioRxiv2019

Generic and context-dependent gene modulations during Hydra whole body regeneration

The cnidarian Hydra is a classical model of whole-body regeneration. Historically, Hydra apical regeneration has received more attention than its basal counterpart, most studies considering these two regenerative processes independently. We present here a transcriptome-wide comparative analysis of apical and basal regeneration after decapitation and mid-gastric bisection, augmented with a characterization of positional and cell-type expression patterns in non-regenerating animals. The profiles of 25637 Hydra transcripts are available on HydrATLAS (https://hydratlas.unige.ch), a web interface allowing a convenient access to each transcript profile. These data indicate that generic impulse-type modulations occur during the first four hours post-amputation, consistent with a similar integration of injury-related cues on both sides of the amputation plane. Initial divergences in gene regulations are observed in regenerating tips between four and eight hours post-amputation, followed by a dramatic transcriptomic reprogramming between eight and 16 hours when regulations become sustained. As expected, central components of apical patterning, Wnt3 and HyBra1, are among the earliest genes up-regulated during apical regeneration. During early basal regeneration, a BMP signaling ligand (BMP5-8c) and a potential BMP inhibitor (NBL1) are up-regulated, suggesting that BMP signaling is involved in the basal organizer, as supported by higher levels of phosphorylated Smad in the basal region and by the LiCl-induced extension of NBL1 expression. By contrast, upon ectopic activation of Wnt/{beta}-catenin signaling, NBL1 is no longer expressed, basal differentiation is not maintained and basal regeneration is abolished. A tight cross-talk between Wnt/{beta}-catenin apically and BMP signaling basally appears necessary for maintaining and regenerating Hydra anatomy.

developmental biology↗

bioRxiv2018

An evolutionary-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra

The Hydra polyp regenerates its head by transforming the gastric tissue below the wound into a head organizer made of two antagonistic cross-reacting components. The activator, previously characterized as Wnt3, drives apical differentiation by acting locally and auto-catalytically. The uncharacterized inhibitor, produced under the control of the activator, prevents ectopic head formation. By crossing RNA-seq data obtained in a {beta}-catenin(RNAi) screen performed in planarians and a quantitative analysis of positional and temporal gene expression in Hydra, we identified Sp5 as a transcription factor that fulfills the head inhibitor properties: a Wnt/{beta}-catenin inducible expression, a graded apical-to-basal expression, a sustained up-regulation during head regeneration, a multi-headed phenotype when knocked-down, a repressing activity on Wnt3 expression. In mammalian cells, Hydra and zebrafish Sp5 repress Wnt3 promoter activity while Hydra Sp5 also auto-activates its expression, possibly via {beta}-catenin and/or Tcf/Lef1 interaction. This work identifies Sp5 as a novel potent feedback loop inhibitor of Wnt/{beta}-catenin signaling across eumetazoans.

developmental biology↗

bioRxiv2017

Hydra, a model system for deciphering the mechanisms of aging and resistance to aging

The freshwater cnidarian polyp named Hydra, which can be mass-cultured in the laboratory, is characterized by a highly dynamic homeostasis with a continuous self-renewal of its three adult stem cell populations, the epithelial stem cells from the epidermis, the epithelial stem cells from the gastrodermis, and the multipotent interstitial stem cells, which provide cells of the nervous system, gland cells and germ cells. Two unusual features characterize these stem cells that cannot replace each other, they all avoid G1 to pause in G2, and the two epithelial populations are concomitantly multifunctional and stem cells. H. vulgaris that does not show any signs of aging over the years, resists to weeks of starvation and adapts to the loss of neurogenesis, providing a unique model system to study the resistance to aging. By contrast some strains of a distinct species named H. oligactis undergo a rapid aging process when undergoing gametogenesis or when placed in stress conditions. The aging phenotype is characterized by the rapid loss of somatic interstitial stem cells, the progressive reduction in epithelial stem cell self-renewal, the loss of regeneration, the disorganization of the neuro-muscular system, the loss of the feeding behavior, and the death of all animals within about three months. We review here the possible mechanisms that help H. vulgaris to sustain stem cell self-renewal and thus bypass aging processes. For this, FoxO seems to act as a pleiotropic actor, regulating stem cell proliferation, stress response and apoptosis. In H. oligactis, the regulation of the autophagy flux differs between aging-sensitive and aging-resistant animals, pointing to a key role for proteostasis in the maintenance of a large pool of active and plastic epithelial stem cells.

evolutionary biology↗