Life sciences · 2025
Ciao3 knockout causes acute lung injury through immune activation using single cell sequencing.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Peng Jie, Wang Chunying, Liu Ting, Fan Yingzi, Wang Jian, Zhang Xianwei, Xu Ying, Liu Hongzhou
Аннотация
BACKGROUND: CIAO3 mutation is identified as the causative gene for diffuse pulmonary arteriovenous malformations (dPAVMs). A homozygote patient is follow-up and she is suffering from a cytokine storm. We conduct Ciao3 conditional knockout in endothelial cells (EC-CKO) of mice to clarify its potential roles.
METHODS: The cytokine levels of the homozygote patient and the EC-CKO mice are measured. Bulk RNA sequencing (RNA-seq) and single cell RNA sequencing (scRNA-seq) are performed. R Seurat package and cellmarker 2.0 are used to cluster and annotate the data. The differential, enrichment, protein interaction, and cell communication analyses are conducted.
RESULTS: The patient is suffering from a cytokine storm. Ciao3 knockout contributes to increased cytokine levels and acute lung injury (ALI) in mice, indicating activation of immune functions. Inhibition of TNF-α reverses the development of ALI, which reveals that the ALI is caused by inflammatory activation. RNA-seq of whole blood cell shows that inflammatory genes and pathways are upregulated in EC-CKO mice, and inhibition of TNF-α improves the effect of Ciao3 knockout. scRNA-seq of lung tissues displays complex changes in immune cell populations, which leads to abnormal cell-cell communication between ECs and immune cells. Outgoing and incoming signaling analyses suggest that CypA, FN1, and THBS signaling pathway are the main changed pathways, and the monocytes and macrophages are the central effector in EC-CKO mice. Upregulation of CypA and infiltration of macrophages are confirmed by immunohistochemistry.
CONCLUSION: Ciao3 knockout causes ALI through immune activation in mice. The monocytes and macrophages are the central effector and should be further researched.
METHODS: The cytokine levels of the homozygote patient and the EC-CKO mice are measured. Bulk RNA sequencing (RNA-seq) and single cell RNA sequencing (scRNA-seq) are performed. R Seurat package and cellmarker 2.0 are used to cluster and annotate the data. The differential, enrichment, protein interaction, and cell communication analyses are conducted.
RESULTS: The patient is suffering from a cytokine storm. Ciao3 knockout contributes to increased cytokine levels and acute lung injury (ALI) in mice, indicating activation of immune functions. Inhibition of TNF-α reverses the development of ALI, which reveals that the ALI is caused by inflammatory activation. RNA-seq of whole blood cell shows that inflammatory genes and pathways are upregulated in EC-CKO mice, and inhibition of TNF-α improves the effect of Ciao3 knockout. scRNA-seq of lung tissues displays complex changes in immune cell populations, which leads to abnormal cell-cell communication between ECs and immune cells. Outgoing and incoming signaling analyses suggest that CypA, FN1, and THBS signaling pathway are the main changed pathways, and the monocytes and macrophages are the central effector in EC-CKO mice. Upregulation of CypA and infiltration of macrophages are confirmed by immunohistochemistry.
CONCLUSION: Ciao3 knockout causes ALI through immune activation in mice. The monocytes and macrophages are the central effector and should be further researched.