The population context is a driver of the heterogeneous response of epithelial cells to interferons.

IF 8.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Systems Biology Pub Date : 2024-03-01 Epub Date: 2024-01-25 DOI:10.1038/s44320-024-00011-2
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
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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.

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种群背景是上皮细胞对干扰素作出不同反应的驱动因素。
同源细胞对干扰素的反应是异质的。我们采用微图案方法,结合高内容成像和空间分析,描述了上皮细胞的群体背景(细胞相对于邻近细胞的位置)如何影响它们对干扰素的反应。我们发现,位于细胞集落边缘的细胞比嵌入集落内的细胞反应更强。我们确定,干扰素反应的这种空间异质性是由极化的基底侧干扰素受体分布造成的,这使得位于细胞集落中心的细胞对异位干扰素刺激的反应较弱。这一点在细胞系和源自上皮组织的原代细胞中是一致的。重要的是,顶端干扰素处理并不能保护嵌入细胞集落内的细胞免受病毒感染,这表明群体背景驱动的对干扰素的异质性反应会影响病毒感染的结果。我们的数据强调,孤立细胞的行为并不能直接转化为它们在群体中的行为,因此群体背景是影响上皮细胞干扰素反应异质性的一个重要因素。
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来源期刊
Molecular Systems Biology
Molecular Systems Biology 生物-生化与分子生物学
CiteScore
18.50
自引率
1.00%
发文量
62
审稿时长
6-12 weeks
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.
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