Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans

Summary: 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 experi...

Full description

Saved in:
Bibliographic Details
Main Authors: Alicja Brożek, Arianna Ceccarelli, Andreas Christ Sølvsten Jørgensen, Mark Hintze, Vahid Shahrezaei, Michalis Barkoulas
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225000860
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary: 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.
ISSN:2589-0042