Publications by authors named "Ulysse Herbach"

Article Synopsis
  • * Understanding the gene regulatory networks (GRNs) involved in B cell development can shed light on these pathologies, especially with advancements in single-cell transcriptomics that provide detailed gene expression data.
  • * A stochastic model was developed to analyze the influence of key gene regulators (BCL6, IRF4, BLIMP1) and external signals (BCR and CD40) on B cell differentiation, successfully matching mRNA levels seen in different B cell stages, which may help validate GRN structures and improve our understanding of regulatory
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Background: Endometriosis is a chronic disease characterized by growth of endometrial tissue outside the uterine cavity which could affect 200 million women (The term "woman" is used for convenience. Individuals gendered as man or as nonbinary can also suffer from this disease) worldwide. One of the most common symptoms of endometriosis is pelvic chronic pain associated with fatigue.

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Single-cell studies have demonstrated the presence of significant cell-to-cell heterogeneity in gene expression. Whether such heterogeneity is only a bystander or has a functional role in the cell differentiation process is still hotly debated. In this study, we quantified and followed single-cell transcriptional uncertainty - a measure of gene transcriptional stochasticity in single cells - in 10 cell differentiation systems of varying cell lineage progressions, from single to multi-branching trajectories, using the stochastic two-state gene transcription model.

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The rise of single-cell data highlights the need for a nondeterministic view of gene expression, while offering new opportunities regarding gene regulatory network inference. We recently introduced two strategies that specifically exploit time-course data, where single-cell profiling is performed after a stimulus: HARISSA, a mechanistic network model with a highly efficient simulation procedure, and CARDAMOM, a scalable inference method seen as model calibration. Here, we combine the two approaches and show that the same model driven by transcriptional bursting can be used simultaneously as an inference tool, to reconstruct biologically relevant networks, and as a simulation tool, to generate realistic transcriptional profiles emerging from gene interactions.

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Background: Inference of gene regulatory networks from gene expression data has been a long-standing and notoriously difficult task in systems biology. Recently, single-cell transcriptomic data have been massively used for gene regulatory network inference, with both successes and limitations.

Results: In the present work we propose an iterative algorithm called WASABI, dedicated to inferring a causal dynamical network from time-stamped single-cell data, which tackles some of the limitations associated with current approaches.

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Background: The recent development of single-cell transcriptomics has enabled gene expression to be measured in individual cells instead of being population-averaged. Despite this considerable precision improvement, inferring regulatory networks remains challenging because stochasticity now proves to play a fundamental role in gene expression. In particular, mRNA synthesis is now acknowledged to occur in a highly bursty manner.

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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 a peak in gene expression variability at the point of fate commitment. We have tested this hypothesis at the single-cell level by analyzing primary chicken erythroid progenitors through their differentiation process and measuring the expression of selected genes at six sequential time-points after induction of differentiation. In contrast to population-based expression data, single-cell gene expression data revealed a high cell-to-cell variability, which was masked by averaging.

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