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Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice

In this study, we executed single-cell RNA sequencing of intestinal crypts. We analyzed the differentially expressed genes (DEGs) at different time points (the first, third, and fifth days) after 13 Gy and 15 Gy abdominal body radiation (ABR) exposure and then executed gene ontology (GO) enrichment...

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Autores principales: Yuan, Tong, Zhang, Junling, Zhao, Yue, Guo, Yuying, Fan, Saijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638071/
https://www.ncbi.nlm.nih.gov/pubmed/37918127
http://dx.doi.org/10.1016/j.redox.2023.102942
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author Yuan, Tong
Zhang, Junling
Zhao, Yue
Guo, Yuying
Fan, Saijun
author_facet Yuan, Tong
Zhang, Junling
Zhao, Yue
Guo, Yuying
Fan, Saijun
author_sort Yuan, Tong
collection PubMed
description In this study, we executed single-cell RNA sequencing of intestinal crypts. We analyzed the differentially expressed genes (DEGs) at different time points (the first, third, and fifth days) after 13 Gy and 15 Gy abdominal body radiation (ABR) exposure and then executed gene ontology (GO) enrichment analysis, RNA velocity analysis, cell communication analysis, and ligand‒receptor interaction analysis to explore the vital events in damage repair and the multiple effects of the Wnt3/β-catenin pathway on irradiated mice. Results from bioinformatics analysis were confirmed by a series of biological experiments. Results showed that the antibacterial response is a vital event during the damage response process after 13 Gy ABR exposure; ionizing radiation (IR) induced high heterogeneity in the transient amplification (TA) cluster, which may differentiate into mature cells and stem cells in irradiated small intestine (SI) crypts. Conducting an enrichment analysis of the DEGs between mice exposed to 13 Gy and 15 Gy ABR, we concluded that the Wnt3/β-catenin and MIF-CD74/CD44 signaling pathways may contribute to 15 Gy ABR-induced mouse death. Wnt3/β-catenin promotes the recovery of irradiated SI stem/progenitor cells, which may trigger macrophage migration inhibitory factor (MIF) release to further repair IR-induced SI injury; however, with the increase in radiation dose, activation of CD44 on macrophages provides the receptor for MIF signal transduction, initiating the inflammatory cascade response and ultimately causing a cytokine release syndrome. In contrast to previous research, we confirmed that inhibition of the Wnt3/β-catenin pathway or blockade of CD44 on the second day after 15 Gy ABR may significantly protect against ABR-induced death. This study indicates that the Wnt3/β-catenin pathway plays multiple roles in damage repair after IR exposure; we also propose a novel point that the interaction between intestinal crypt stem cells (ISCs) and macrophages through the MIF-CD74/CD44 axis may exacerbate SI damage in irradiated mice.
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spelling pubmed-106380712023-11-11 Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice Yuan, Tong Zhang, Junling Zhao, Yue Guo, Yuying Fan, Saijun Redox Biol Research Paper In this study, we executed single-cell RNA sequencing of intestinal crypts. We analyzed the differentially expressed genes (DEGs) at different time points (the first, third, and fifth days) after 13 Gy and 15 Gy abdominal body radiation (ABR) exposure and then executed gene ontology (GO) enrichment analysis, RNA velocity analysis, cell communication analysis, and ligand‒receptor interaction analysis to explore the vital events in damage repair and the multiple effects of the Wnt3/β-catenin pathway on irradiated mice. Results from bioinformatics analysis were confirmed by a series of biological experiments. Results showed that the antibacterial response is a vital event during the damage response process after 13 Gy ABR exposure; ionizing radiation (IR) induced high heterogeneity in the transient amplification (TA) cluster, which may differentiate into mature cells and stem cells in irradiated small intestine (SI) crypts. Conducting an enrichment analysis of the DEGs between mice exposed to 13 Gy and 15 Gy ABR, we concluded that the Wnt3/β-catenin and MIF-CD74/CD44 signaling pathways may contribute to 15 Gy ABR-induced mouse death. Wnt3/β-catenin promotes the recovery of irradiated SI stem/progenitor cells, which may trigger macrophage migration inhibitory factor (MIF) release to further repair IR-induced SI injury; however, with the increase in radiation dose, activation of CD44 on macrophages provides the receptor for MIF signal transduction, initiating the inflammatory cascade response and ultimately causing a cytokine release syndrome. In contrast to previous research, we confirmed that inhibition of the Wnt3/β-catenin pathway or blockade of CD44 on the second day after 15 Gy ABR may significantly protect against ABR-induced death. This study indicates that the Wnt3/β-catenin pathway plays multiple roles in damage repair after IR exposure; we also propose a novel point that the interaction between intestinal crypt stem cells (ISCs) and macrophages through the MIF-CD74/CD44 axis may exacerbate SI damage in irradiated mice. Elsevier 2023-10-25 /pmc/articles/PMC10638071/ /pubmed/37918127 http://dx.doi.org/10.1016/j.redox.2023.102942 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Yuan, Tong
Zhang, Junling
Zhao, Yue
Guo, Yuying
Fan, Saijun
Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice
title Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice
title_full Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice
title_fullStr Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice
title_full_unstemmed Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice
title_short Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice
title_sort single-cell rna sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the wnt3/β-catenin pathway in irradiated mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638071/
https://www.ncbi.nlm.nih.gov/pubmed/37918127
http://dx.doi.org/10.1016/j.redox.2023.102942
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