A5031225061- Genomics and Chromatin Dynamics
- Platelet Disorders and Treatments
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Developmental Biology and Gene Regulation
- Renal Diseases and Glomerulopathies
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Acute Lymphoblastic Leukemia research
- Immunodeficiency and Autoimmune Disorders
- Plant Molecular Biology Research
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Cytomegalovirus and herpesvirus research
- Cell Adhesion Molecules Research
- Chronic Myeloid Leukemia Treatments
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
- Ocular Disorders and Treatments
- Immunotherapy and Immune Responses
- Wnt/β-catenin signaling in development and cancer
- Neurobiology and Insect Physiology Research
Inserm
2011-2025
Aix-Marseille Université
2012-2024
Centre National de la Recherche Scientifique
2011-2024
Centre d’Immunologie de Marseille-Luminy
2018-2022
KU Leuven
2012-2019
VIB-KU Leuven Center for Brain & Disease Research
2018
Indiana University School of Medicine
2017
Theories and Approaches of Genomic Complexity
2014
Institut de Microbiologie de la Méditerranée
2011
Identifying master regulators of biological processes and mapping their downstream gene networks are key challenges in systems biology. We developed a computational method, called iRegulon, to reverse-engineer the transcriptional regulatory network underlying co-expressed set using cis-regulatory sequence analysis. iRegulon implements genome-wide ranking-and-recovery approach detect enriched transcription factor motifs optimal sets direct targets. increase accuracy inference by very large...
i-cisTarget is a web tool to predict regulators of set genomic regions, such as ChIP-seq peaks or co-regulated/similar enhancers. can also be used identify upstream and their target enhancers starting from co-expressed genes. Whereas the original version was focused on Drosophila data, 2015 update provides support for human mouse data. detects transcription factor motifs (position weight matrices) experimental data tracks (e.g. ENCODE, Roadmap Epigenomics) that are enriched in input regions....
The field of regulatory genomics today is characterized by the generation high-throughput data sets that capture genome-wide transcription factor (TF) binding, histone modifications, or DNAseI hypersensitive regions across many cell types and conditions. In this context, a critical question how to make optimal use these publicly available datasets when studying transcriptional regulation. Here, we address in Drosophila melanogaster for which large number are available. We developed...
Genomic enhancers regulate spatio-temporal gene expression by recruiting specific combinations of transcription factors (TFs). When TFs are bound to active regulatory regions, they displace canonical nucleosomes, making these regions biochemically detectable as nucleosome-depleted or accessible/open chromatin. Here we ask whether open chromatin profiling can be used identify the entire repertoire promoters and underlying tissue-specific during normal development oncogenesis in vivo. To this...
Abstract Chimeric antigen receptor T cell (CAR-T) targeting the CD19 represents an innovative therapeutic approach to improve outcome of relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Yet, despite a high initial remission rate, CAR-T therapy ultimately fails for some patients. Notably, around half relapsing patients develop negative (CD19 neg ) B-ALL allowing leukemic cells evade CD19-targeted therapy. Herein, we investigate patient, at two-time points: before (T1) and...
are validated by ChIP-seq and correlate with chromatin opening
During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here, we combine whole-genome transcriptional epigenetic analyses with in vivo functional studies demonstrate that Bcl6, a repressor previously reported promote cortical acts as driver neurogenic transition direct silencing selective repertoire genes belonging multiple pathways promoting self-renewal, most...
Germline variants of FLI1, essential for megakaryopoiesis, are linked to bleeding disorders, platelet aggregation defects and mild thrombocytopenia. However, the mechanisms behind these abnormalities remain unclear. This study aims elucidate impact FLI1 on human megakaryocytes platelets. We focused four variants, two which novel (p.G307R p.R340C). assessed megakaryopoiesis using single-cell RNA sequencing were confirmed in patient platelets cell lines. Results showed p.R337Q, p.K345E p.R340C...
The identification of transcription factor binding sites, enhancers, and transcriptional target genes often relies on the integration gene expression profiling computational cis -regulatory sequence analysis. Methods for prediction elements can take advantage comparative genomics to increase signal-to-noise levels. However, data are usually derived from only one species. Here we investigate tissue-specific cross-species by high-throughput sequencing, combined with motif discovery. First,...
Proper organ patterning depends on a tight coordination between cell proliferation and differentiation. The of Drosophila retina occurs both very fast with high precision. This process is driven by the dynamic changes in signaling activity conserved Hedgehog (Hh) pathway, which coordinates fate determination, cycle tissue morphogenesis. Here we show that during retinogenesis, retinal determination gene dachshund (dac) not only target Hh but also modulator its activity. Using developmental...
In the thymus, T cell progenitors differentiate in order to generate naive lymphocytes which migrate periphery where they will fulfill their function adaptive immune response. During thymopoiesis, genomic alterations thymocytes can promote leukemia development. Among recurrent alteration is PTEN inactivation, associated MYC overexpression. Herein, we used conditional Pten and Myc knockout mouse models single-cell RNA-sequencing approach, investigate impact of loss on physio-pathological...
The specification and growth of organs is controlled simultaneously by networks transcription factors. While the connection between these factors with fate determinants increasingly clear, how they establish link cell cycle far less understood. Here we investigate this in developing Drosophila eye, where two factors, MEIS1 homologue hth Zn-finger tsh, synergize to stimulate proliferation naïve eye progenitors. Experiments combining transcriptomics, open-chromatin profiling, motif analysis...
Developmental transcriptional regulatory networks are circuits of transcription factors (TFs) and cis-acting DNA elements (Cis Regulatory Modules, CRMs) that dynamically control expression downstream genes. Comprehensive knowledge these is an essential step towards our understanding developmental processes. However, this mostly based on genome-wide mapping factor binding sites, therefore requires prior regarding the TFs involved in network. Focusing how temporal gene integrated within a...
Scoring the impact of noncoding variation on function cis-regulatory regions, their chromatin state, and qualitative quantitative expression levels target genes is a fundamental problem in evolutionary genomics. A particular challenge how to model divergence traits identify relationships between changes across different genome, activity landscape, transcriptome. Here, we examine use Ornstein–Uhlenbeck (OU) infer selection at level predicted modules (CRMs), link these with transcription...
Signaling through the αβT cell receptor (TCR) is a crucial determinant of T-cell fate and can induce two opposite outcomes during thymocyte development: death or survival differentiation. To date, role played by in oncogenic transformation developing T cells remains unclear. Here we show that human primary acute lymphoblastic leukemias expressing an are frequently deficient for phosphatase tensin homolog protein (PTEN), fail to respond strongly activation. Using Pten-deficient leukemia mouse...
PTEN (Phosphatase and TENsin homolog) is a well-known tumor suppressor involved in numerous types of cancer, including T-cell acute lymphoblastic leukemia (T-ALL). In human, loss-of-function mutations are correlated to mature T-ALL expressing receptor (TCR) at their cell surface. accordance with human T-ALL, inactivation Pten gene mouse thymocytes induces TCRαβ+ development. Herein, we explored the functional interaction between TCRαβ signaling PTEN. First, performed single-cell RNA...