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...
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Elsevier
2025-02-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225000860 |
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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 |
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