Biology subjects

Picard, S.

Publications and source records attributed to Picard, S..

8 recordsLinked to original sources

bioRxiv2025

Mapping the visual cortex with Zebra noise and wavelets

Studies of the early visual system often require characterizing the visual preferences of large populations of neurons. This task typically requires multiple stimuli such as sparse noise and drifting gratings, each of which probe only a limited set of visual features. Here we introduce a new dynamic stimulus with sharp-edged stripes called Zebra noise and a new analysis model based on wavelets, and show that in combination they are highly efficient for mapping multiple aspects of the visual preferences of thousands of neurons. We used two-photon calcium imaging to record the activity of neurons in the mouse visual cortex. Zebra noise elicited strong responses that were more repeatable than those evoked by traditional stimuli. The wavelet-based model captured the repeatable aspects of the resulting responses, providing measures of neuronal tuning for multiple stimulus features: position, orientation, size, spatial frequency, drift rate, and direction. The method proved efficient, requiring only 5 minutes of stimulus (repeated 3 times) to characterize the tuning of thousands of neurons across visual areas. In combination, the Zebra noise stimulus and the wavelet-based model provide a broadly applicable toolkit for the rapid characterization of visual representations, promising to accelerate future studies of visual function.

neuroscience↗

bioRxiv2021

Deleting in vivo β-catenin degradation domain in mouse hepatocytes drives hepatocellular carcinoma or hepatoblastoma-like tumors

Background and aimsOne-third of hepatocellular carcinomas (HCCs) have mutations that activate the {beta}-catenin pathway with mostly CTNNB1 mutations. Mouse models using Adenomatous polyposis coli (Apc) loss-of-functions (LOF) are widely used to mimic {beta}-catenin-dependent tumorigenesis. Considering the low prevalence of APC mutations in human HCCs we aimed to generate hepatic tumors through CTNNB1 exon 3 deletion ({beta}cat{Delta}ex3) and to compare them to hepatic tumors with Apc LOF engineered through a frameshift in exon 15 (Apcfs-ex15). MethodsWe used hepatic-specific and inducible Cre-lox mouse models as well as a hepatic-specific in vivo CRISPR/Cas9 approach using AAV vectors, to generate Apcfs-ex15 and {beta}cat{Delta}ex3 hepatic tumors harboring activation of the {beta}-catenin pathway. Tumors generated by the Cre-lox models were analyzed phenotypically using immunohistochemistry and were selected for transcriptomic analysis using RNA-sequencing. Mouse RNAseq data were compared to human RNAseq data (normal tissues (8), HCCs (48) and hepatoblastomas (9)) in an integrative analysis. Tumors generated via CRISPR were analyzed using DNA sequencing and immunohistochemistry. ResultsMice with {beta}cat{Delta}ex3 alteration in hepatocytes developed liver tumors. Generated tumors were indistinguishable from those arising in Apcfs-ex15 mice. Both Apcfs-ex15 and {beta}cat{Delta}ex3 mouse models induced two phenotypically distinct tumors (differentiated or undifferentiated). Integrative analysis of human and mouse tumors showed that mouse differentiated tumors are close to human well differentiated CTNNB1-mutated tumors, while undifferentiated ones are closer to human mesenchymal hepatoblastomas, and are activated for YAP signaling. ConclusionApcfs-ex15 and {beta}cat{Delta}ex3 mouse models similarly induce tumors transcriptionally close to either well differentiated {beta}-Catenin activated human HCCs or mesenchymal hepatoblastomas.

cancer biology↗

bioRxiv2019

ExpressWeb: A Web application for clustering and visualization of expression data.

The recent explosion of transcriptomics and proteomic data have resulted in vast amounts of datasets without connection and sometime too large to be easily analysed. Integration between datasets and analysis of an extracted datasets are limiting factors which need to be solved in order to make full use of the data and to connect data.\n\nExpressWeb is an online web tool that combines a Taylor clustering of expressed data sets to extract gene network with gene annotations to visualise the co-expression network. Data sets can become from personal or publically experiments. ExpressWeb allows to easily compute clustering on expression data and provides friendly and useful visualisation tools as heatmaps, graphs and networks, generating output images which can be used for scientific publications.

bioinformatics↗

bioRxiv2019

TM3’seq: a tagmentation-mediated 3’ sequencing approach for improving scalability of RNA-seq experiments

RNA-seq has become the standard tool for collecting genome-wide expression data in diverse fields, from quantitative genetics and medical genomics to ecology and developmental biology. However, RNA-seq library preparation is still prohibitive for many laboratories. Recently, the field of single-cell transcriptomics has reduced costs and increased throughput by adopting early barcoding and pooling of individual samples --producing a single final library containing all samples. In contrast, RNA-seq protocols where each sample is processed individually are significantly more expensive and lower throughput than single-cell approaches. Yet, many projects depend on individual library generation to preserve important samples or for follow-up re-sequencing experiments. Improving on currently available RNA-seq methods we have developed TM3seq, a 3-enriched library preparation protocol that uses Tn5 transposase and preserves sample identity at each step. TM3seq is designed for high-throughput processing of individual samples (96 samples in 6h, with only 3h hands-on time) at a fraction of the cost of commercial kits ($1.5 per sample). The protocol was tested in a range of human and Drosophila melanogaster RNA samples, recovering transcriptomes of the same quality and reliability than the commercial NEBNext(R) kit. We expect that the cost-and time-efficient features of TM3seq make large-scale RNA-seq experiments more permissive for the entire scientific community.

genomics↗

bioRxiv2018

Action perception recruits the cerebellum and is impaired in spinocerebellar ataxia patients

Our cerebellum has been proposed to generate prediction signals that may help us plan and execute our motor programs. However, to what extent our cerebellum is also actively involved in perceiving the action of others remains to be elucidated. Using fMRI, we show here that observing goal-directed hand actions of others bilaterally recruits cerebellar Lobules VI, VIIb and VIIIa. Moreover, whereas healthy subjects (n=31) were found to be able to discriminate subtle differences in the kinematics of observed limb movements of others, patients suffering from spinocerebellar ataxia type 6 (SCA6; n=21) were severely impaired in performing such tasks. Our data suggest that the human cerebellum is actively involved in perceiving the kinematics of the hand actions of others and that SCA6 patients deficits include a difficulty in perceiving the actions of other individuals. This finding alerts us to the fact that cerebellar disorders can alter social cognition. Given that impairments in social cognition have been reported to be one of the most debilitating consequences of neurological disorders, this finding may be relevant to improving the quality of life of patients and their families.

neuroscience↗

bioRxiv2018

A genetic, genomic, and computational resource for exploring neural circuit function

The anatomy of many neural circuits is being characterized with increasing resolution, but their molecular properties remain mostly unknown. Here, we characterize gene expression patterns in distinct neural cell types of the Drosophila visual system using genetic lines to access individual cell types, the TAPIN-seq method to measure their transcriptomes, and a probabilistic method to interpret these measurements. We used these tools to build a resource of high-resolution transcriptomes for 100 driver lines covering 67 cell types, available at http://www.opticlobe.com. Combining these transcriptomes with recently reported connectomes helps characterize how information is transmitted and processed across a range of scales, from individual synapses to circuit pathways. We describe examples that include identifying neurotransmitters, including cases of co-release, generating functional hypotheses based on receptor expression, as well as identifying strong commonalities between different cell types.\n\nHighlightsO_LITranscriptomes reveal transmitters and receptors expressed in Drosophila visual neurons\nC_LIO_LITandem affinity purification of intact nuclei (TAPIN) enables neuronal genomics\nC_LIO_LITAPIN-seq and genetic drivers establish transcriptomes of 67 Drosophila cell types\nC_LIO_LIProbabilistic modeling simplifies interpretation of large transcriptome catalogs\nC_LI

neuroscience↗

bioRxiv2017

The Transcriptional Logic of Mammalian Neuronal Diversity

The mammalian nervous system is constructed of many cell types, but the principles underlying this diversity are poorly understood. To assess brain-wide transcriptional diversity, we sequenced the transcriptomes of the largest collection of genetically and anatomically identified neuronal classes. Using improved expression metrics that distinguish information content from signal-to-noise-ratio, we found that homeobox transcription factors contain the highest information about cell types and have the lowest noise. Genes that contribute the most to neuronal diversity tend to be long and enriched in factors specifically involved in neuronal function. Genome accessibility measurements reveal that long genes have more candidate regulatory elements arrayed in more distinct patterns. These elements frequently overlap interspersed repeats (mobile elements) and the pattern of repeats is predictive of gene expression. New regulatory sites resulting from elongation of neuronal genes by mobile elements may be an evolutionary force enhancing nervous system complexity.

neuroscience↗

bioRxiv2016

Genetic and transgenic reagents for Drosophila simulans, D.mauritiana, D. yakuba, D. santomea and D. virilis

Species of the Drosophila melanogaster species subgroup, including the species D. simulans, D. mauritiana, D. yakuba, and D. santomea, have long served as model systems for studying evolution. Studies in these species have been limited, however, by a paucity of genetic and transgenic reagents. Here we describe a collection of transgenic and genetic strains generated to facilitate genetic studies within and between these species. We have generated many strains of each species containing mapped piggyBac transposons including an enhanced yellow fluorescent protein gene expressed in the eyes and a phiC31 attP site-specific integration site. We have tested a subset of these lines for integration efficiency and reporter gene expression levels. We have also generated a smaller collection of other lines expressing other genetically encoded fluorescent molecules in the eyes and a number of other transgenic reagents that will be useful for functional studies in these species. In addition, we have mapped the insertion locations of 58 transposable elements in D. virilis that will be useful for genetic mapping studies.

genetics↗