A5089245484- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Erythrocyte Function and Pathophysiology
- Cell Image Analysis Techniques
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Data Mining Algorithms and Applications
- Genomics and Chromatin Dynamics
- Virus-based gene therapy research
- Mathematical Biology Tumor Growth
- Retinoids in leukemia and cellular processes
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Animal Virus Infections Studies
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Evolution and Genetic Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Blood properties and coagulation
- Animal Genetics and Reproduction
- Ubiquitin and proteasome pathways
Université Claude Bernard Lyon 1
2016-2025
Inserm
2016-2025
École Normale Supérieure de Lyon
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Lyon College
2025
institut Camille-Jordan
2011-2024
Institut national de recherche en informatique et en automatique
2015-2024
Centre Inria de l'Université Grenoble Alpes
2015-2024
Institut Jacques Monod
2024
Laboratoire de Biologie et Modélisation de la Cellule
1992-2023
Activation of naive CD8 T-cells can lead to the generation multiple effector and memory subsets. Multiple parameters associated with activation conditions are involved in generating this diversity that is heterogeneous molecular contents activated cells. Although cell polarisation upon antigenic stimulation resulting asymmetric division known be a major source heterogeneity fate regulation, consequences stochastic uneven partitioning content subsequent divisions remain unclear yet. Here we...
In some recent studies, a view emerged that stochastic dynamics governing the switching of cells from one differentiation state to another could be characterized by peak in gene expression variability at point fate commitment. We have tested this hypothesis single-cell level analyzing primary chicken erythroid progenitors through their process and measuring selected genes six sequential time-points after induction differentiation. contrast population-based data, data revealed high...
Single cell transcriptional profiling opens up a new avenue in studying the functional role of cell-to-cell variability physiological processes. The analysis single expression profiles creates challenges due to distributive nature data and stochastic dynamics gene transcription process. reconstruction regulatory networks (GRNs) using is particularly challenging, especially when directed gene-gene relationships are desired.We developed SINCERITIES (SINgle CEll Regularized Inference...
The association-rules discovery (ARD) technique has yet to be applied gene-expression data analysis. Even in the absence of previous biological knowledge, it should identify sets genes whose expression is correlated. first association-rule miners appeared six years ago and proved efficient at dealing with sparse weakly correlated data. A huge international research effort led new algorithms for tackling difficult contexts these are particularly suited analysis large matrices. To validate ARD...
The recent development of single-cell transcriptomics has enabled gene expression to be measured in individual cells instead being population-averaged. Despite this considerable precision improvement, inferring regulatory networks remains challenging because stochasticity now proves play a fundamental role expression. In particular, mRNA synthesis is acknowledged occur highly bursty manner. We propose view the inference problem as fitting procedure for mechanistic network model that...
The rise of single-cell data highlights the need for a nondeterministic view gene expression, while offering new opportunities regarding regulatory network inference. We recently introduced two strategies that specifically exploit time-course data, where profiling is performed after stimulus: HARISSA, mechanistic model with highly efficient simulation procedure, and CARDAMOM, scalable inference method seen as calibration. Here, we combine approaches show same driven by transcriptional...
Gene promoters can be in various epigenetic states and undergo interactions with many molecules a highly transient, probabilistic combinatorial way, resulting complex global dynamics as observed experimentally. However, models of stochastic gene expression commonly consider promoter activity two-state on/off system. We here model single-gene that represent arbitrary prokaryotic or eukaryotic promoters, based on the interplay between factors, including energy-dependent remodeling enzymatic...
Individual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterising transcriptional changes cord blood-derived CD34+ at the single-cell level and integrating data with cell division history morphological determined time-lapse microscopy. show major leading to multilineage-primed gene expression state occur very rapidly during first cycle. One of 2 stable lineage-primed patterns emerges gradually each variable timing. Some reach...
Inference of gene regulatory networks from expression data has been a long-standing and notoriously difficult task in systems biology. Recently, single-cell transcriptomic have massively used for network inference, with both successes limitations.In the present work we propose an iterative algorithm called WASABI, dedicated to inferring causal dynamical time-stamped data, which tackles some limitations associated current approaches. We first introduce concept waves, posits that information...
Abstract Background Mature blood cells arise from hematopoietic stem in the bone marrow by a process of differentiation along one several different lineage trajectories. This is often represented as series discrete steps increasing progenitor cell commitment to given lineage, but for general, whether instructive or stochastic remains controversial. Here, we examine this question analyzing single-cell transcriptomic data human cells, assessing cell-to-cell variability trajectories into four...
Abstract Background A number of studies have established that stochasticity in gene expression may play an important role many biological phenomena. This therefore calls for further investigations to identify the molecular mechanisms at stake, order understand and manipulate cell-to-cell variability. In this work, we explored played by chromatin dynamics regulation stochastic higher eukaryotic cells. Results For purpose, generated isogenic chicken-cell populations expressing a fluorescent...
Despite the stochastic noise that characterizes all cellular processes cells are able to maintain and transmit their daughter stable level of gene expression. In order better understand this phenomenon, we investigated temporal dynamics expression variation using a double reporter model. We compared cell clones with transgenes coding for highly mRNA fluorescent proteins expressing destabilized mRNA-s proteins. Both types displayed strong heterogeneity levels. However, products produced...
Abstract Memory CD8 T cells typically exhibit improved effector functions compared to their naive counterparts. However, under certain activation conditions, such as chronic viral infections or cancer, these may develop functional defects. In this study, we the quality of memory generated following tumor rejection with those arising from an acute infection. We found that tumor-induced (Tum-CD8) exhibited a distinct phenotype and transcriptomic profile viral-induced (Vir-CD8) cells. These are...
Neuroblastoma is a malignant childhood cancer with significant inter- and intrapatient heterogeneity, arising from abnormal differentiation of neural crest cells into sympathetic neurons. The lack actionable mutations limits therapeutic options, highlighting the need to better understand molecular mechanisms driving this differentiation. While RNA velocity has provided some insights, it limited in modeling regulatory relationships. To address this, we applied our integrated Gene Regulatory...
<title>Abstract</title> In the preimplantation mammalian embryo, stochastic cell-to-cell expression heterogeneity is followed by signal reinforcement to initiate specification of Inner Cell Mass (ICM) cells into Epiblast (Epi). The NANOG, key transcription factor for Epi fate, necessary but not sufficient: coincident other factors required. To identify <italic>Nanog</italic>-helper genes, we analyzed gene variability in five time-stamped single-cell transcriptomic datasets using differential...
Invasion of the vector salivary glands by Plasmodium is a critical step for malaria transmission. To describe gland cellular responses to sporozoite invasion, we have undertaken analysis Anopheles gambiae transcriptome using Serial Analysis Gene Expression (SAGE). Statistical more than 160000 sequenced tags generated from four libraries, two infected berghei, controls, revealed that at least 57 genes are differentially expressed in glands. Among 37 immune-related identified SAGE tags,...
Our previous single-cell based gene expression analysis pointed out significant variations of LDHA level during erythroid differentiation. Deeper investigations highlighted that a metabolic switch occurred along differentiation cells. More precisely we showed self-renewing progenitors relied mostly upon lactate-productive glycolysis, and required activity, whereas differentiating cells, mainly involved mitochondrial oxidative phosphorylation (OXPHOS). These rearrangements were coming with...
To better understand the mechanisms behind cells decision-making to differentiate, we assessed influence of stochastic gene expression (SGE) modulation on erythroid differentiation process. It has been suggested that a role in cell fate which is revealed by single-cell analyses but studies dedicated demonstrate consistency this link are still lacking. Recent observations showed SGE significantly increased during and few an increase level accompanied However, consistent relation both...
Chronic myelogenous leukemia arises from the transformation of hematopoietic stem cells by BCR-ABL oncogene. Though transformed are predominantly BCR-ABL-dependent and sensitive to tyrosine kinase inhibitor treatment, some BMPR1B+ leukemic treatment-insensitive rely, among others, on bone morphogenetic protein (BMP) pathway for their survival via a BMP4 autocrine loop. Here, we further studied involvement BMP signaling in favoring residual cell persistence marrow patients having achieved...