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!
_version_ 1825206897284743168
author Alicja Brożek
Arianna Ceccarelli
Andreas Christ Sølvsten Jørgensen
Mark Hintze
Vahid Shahrezaei
Michalis Barkoulas
author_facet Alicja Brożek
Arianna Ceccarelli
Andreas Christ Sølvsten Jørgensen
Mark Hintze
Vahid Shahrezaei
Michalis Barkoulas
author_sort Alicja Brożek
collection DOAJ
description 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.
format Article
id doaj-art-b1de906672d443bf9bf8121566eb95f7
institution Kabale University
issn 2589-0042
language English
publishDate 2025-02-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-b1de906672d443bf9bf8121566eb95f72025-02-07T04:48:02ZengElsevieriScience2589-00422025-02-01282111826Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegansAlicja Brożek0Arianna Ceccarelli1Andreas Christ Sølvsten Jørgensen2Mark Hintze3Vahid Shahrezaei4Michalis Barkoulas5Department of Life Sciences, Imperial College London, London SW7 2AZ, UKDepartment of Mathematics, Imperial College London, London SW7 2BX, UK; Mathematical Institute, University of Oxford, Oxford OX2 6GG, UKDepartment of Mathematics, Imperial College London, London SW7 2BX, UK; I-X Centre for AI In Science, Imperial College London, London W12 0BZ, UKDepartment of Life Sciences, Imperial College London, London SW7 2AZ, UKDepartment of Mathematics, Imperial College London, London SW7 2BX, UK; Corresponding authorDepartment of Life Sciences, Imperial College London, London SW7 2AZ, UK; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225000860BioinformaticsBiological sciencesCell biologyGene network
spellingShingle Alicja Brożek
Arianna Ceccarelli
Andreas Christ Sølvsten Jørgensen
Mark Hintze
Vahid Shahrezaei
Michalis Barkoulas
Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
iScience
Bioinformatics
Biological sciences
Cell biology
Gene network
title Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
title_full Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
title_fullStr Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
title_full_unstemmed Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
title_short Inference of a three-gene network underpinning epidermal stem cell development in Caenorhabditis elegans
title_sort inference of a three gene network underpinning epidermal stem cell development in caenorhabditis elegans
topic Bioinformatics
Biological sciences
Cell biology
Gene network
url http://www.sciencedirect.com/science/article/pii/S2589004225000860
work_keys_str_mv AT alicjabrozek inferenceofathreegenenetworkunderpinningepidermalstemcelldevelopmentincaenorhabditiselegans
AT ariannaceccarelli inferenceofathreegenenetworkunderpinningepidermalstemcelldevelopmentincaenorhabditiselegans
AT andreaschristsølvstenjørgensen inferenceofathreegenenetworkunderpinningepidermalstemcelldevelopmentincaenorhabditiselegans
AT markhintze inferenceofathreegenenetworkunderpinningepidermalstemcelldevelopmentincaenorhabditiselegans
AT vahidshahrezaei inferenceofathreegenenetworkunderpinningepidermalstemcelldevelopmentincaenorhabditiselegans
AT michalisbarkoulas inferenceofathreegenenetworkunderpinningepidermalstemcelldevelopmentincaenorhabditiselegans