Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
File(s)
Published version
Author(s)
Brożek, Alicja
Ceccarelli, Arianna
Jørgensen, Andreas Christ Sølvsten
Hintze, Mark
Shahrezaei, vahid
Type
Journal Article
Abstract
Gene regulatory networks are crucial in cellular decision-making, making the inference of their architecture essential for understanding organismal development. The gene network of Caenorhabditis elegans epidermal stem cells, known as seam cells, remains undefined. Here, we integrate experimental data, mathematical modeling, and statistical inference to investigate this network, focusing on three core transcription factors (TFs), namely ELT-1, EGL-18, and CEH-16. We use single-molecule FISH to quantify TF mRNA levels in single seam cells of wild-type and mutant backgrounds across four early larval stages. Using Modular Response Analysis, we predict TF interactions and uncover a repressive interaction between CEH-16 and egl-18 consistent across time points. We validate its significance at the L1 stage with ordinary differential equations and Bayesian modeling, making testable predictions for a double mutant. Our findings reveal TF regulatory relationships in seam cells and demonstrate a flexible mathematical framework for inferring gene regulatory networks from gene expression data.
Date Issued
2025-02-21
Date Acceptance
2025-01-13
Citation
iScience, 2025, 28 (2)
ISSN
2589-0042
Publisher
Elsevier
Journal / Book Title
iScience
Volume
28
Issue
2
Copyright Statement
© 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.isci.2025.111826
Publication Status
Published
Article Number
ARTN 111826
Date Publish Online
2025-01-16