Camila Metz-Zumaran, Zina M Uckeley, Patricio Doldan, Francesco Muraca, Yagmur Keser, Pascal Lukas, Benno Kuropka, Leonie Küchenhoff, Soheil Rastgou Talemi, Thomas Höfer, Christian Freund, Elisabetta Ada Cavalcanti-Adam, Frederik Graw, Megan Stanifer, Steeve Boulant
{"title":"The population context is a driver of the heterogeneous response of epithelial cells to interferons.","authors":"Camila Metz-Zumaran, Zina M Uckeley, Patricio Doldan, Francesco Muraca, Yagmur Keser, Pascal Lukas, Benno Kuropka, Leonie Küchenhoff, Soheil Rastgou Talemi, Thomas Höfer, Christian Freund, Elisabetta Ada Cavalcanti-Adam, Frederik Graw, Megan Stanifer, Steeve Boulant","doi":"10.1038/s44320-024-00011-2","DOIUrl":null,"url":null,"abstract":"<p><p>Isogenic cells respond in a heterogeneous manner to interferon. Using a micropatterning approach combined with high-content imaging and spatial analyses, we characterized how the population context (position of a cell with respect to neighboring cells) of epithelial cells affects their response to interferons. We identified that cells at the edge of cellular colonies are more responsive than cells embedded within colonies. We determined that this spatial heterogeneity in interferon response resulted from the polarized basolateral interferon receptor distribution, making cells located in the center of cellular colonies less responsive to ectopic interferon stimulation. This was conserved across cell lines and primary cells originating from epithelial tissues. Importantly, cells embedded within cellular colonies were not protected from viral infection by apical interferon treatment, demonstrating that the population context-driven heterogeneous response to interferon influences the outcome of viral infection. Our data highlights that the behavior of isolated cells does not directly translate to their behavior in a population, placing the population context as one important factor influencing heterogeneity during interferon response in epithelial cells.</p>","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":"242-275"},"PeriodicalIF":8.5000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912784/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Systems Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44320-024-00011-2","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/25 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Isogenic cells respond in a heterogeneous manner to interferon. Using a micropatterning approach combined with high-content imaging and spatial analyses, we characterized how the population context (position of a cell with respect to neighboring cells) of epithelial cells affects their response to interferons. We identified that cells at the edge of cellular colonies are more responsive than cells embedded within colonies. We determined that this spatial heterogeneity in interferon response resulted from the polarized basolateral interferon receptor distribution, making cells located in the center of cellular colonies less responsive to ectopic interferon stimulation. This was conserved across cell lines and primary cells originating from epithelial tissues. Importantly, cells embedded within cellular colonies were not protected from viral infection by apical interferon treatment, demonstrating that the population context-driven heterogeneous response to interferon influences the outcome of viral infection. Our data highlights that the behavior of isolated cells does not directly translate to their behavior in a population, placing the population context as one important factor influencing heterogeneity during interferon response in epithelial cells.
期刊介绍:
Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems.
Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.