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Multiomic analysis of monocyte-derived alveolar macrophages in idiopathic pulmonary fibrosis

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Názov: Multiomic analysis of monocyte-derived alveolar macrophages in idiopathic pulmonary fibrosis
Autori: Miaomiao Zhang, Jinghao Zhang, Haisheng Hu, Yuan Zhou, ZhiWei Lin, Hui Jing, Baoqing Sun
Zdroj: J Transl Med
Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-17 (2024)
Informácie o vydavateľovi: Springer Science and Business Media LLC, 2024.
Rok vydania: 2024
Predmety: Male, 0301 basic medicine, Receptors, CXCR4, 0303 health sciences, Research, Gene Expression Profiling, Idiopathic pulmonary fibrosis, Multiomic, Middle Aged, Idiopathic Pulmonary Fibrosis, Monocytes, Monocyte-derived alveolar macrophages, 03 medical and health sciences, Phenotype, Gene Expression Regulation, Lung/pathology [MeSH], Female [MeSH], Humans [MeSH], Middle Aged [MeSH], Lung/metabolism [MeSH], Receptors, CXCR4/genetics [MeSH], Transcription factors, Fibrosis, Idiopathic Pulmonary Fibrosis/metabolism [MeSH], Idiopathic Pulmonary Fibrosis/pathology [MeSH], Monocytes/metabolism [MeSH], Idiopathic Pulmonary Fibrosis/genetics [MeSH], Male [MeSH], Phenotype [MeSH], Gene Expression Profiling [MeSH], Gene Expression Regulation [MeSH], Macrophages, Alveolar/pathology [MeSH], Receptors, CXCR4/metabolism [MeSH], Macrophages, Alveolar/metabolism [MeSH], Macrophages, Alveolar, Medicine, Humans, Female, Lung
Popis: Background Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq analysis has proven valuable in the transcriptome profiling of Mo_AMs, the integration analysis of multi-omics may provide additional dimensions of understanding of these cellular populations. Methods We performed multi-omics analysis on 116 scRNAseq, 119 bulkseq and five scATACseq lung tissue samples from IPF. We built a large-scale IPF scRNAseq atlas and conducted the Monocle 2/3 as well as the Cellchat to explore the developmental path and intercellular communication on Mo_AMs. We also reported the difference in metabolisms, tissue repair and phagocytosis between Mo_AMs and tissue-resident alveolar macrophages (TRMs). To determine whether Mo_AMs affected pulmonary function, we projected clinical phenotypes (FVC%pred) from the bulkseq dataset onto the scRNAseq atlas. Finally, we used scATATCseq to uncover the upstream regulatory mechanisms and determine key drivers in Mo_AMs. Results We identified three Mo_AMs clusters and the trajectory analysis further validated the origin of these clusters. Moreover, via the Cellchat analysis, the CXCL12/CXCR4 axis was found to be involved in the molecular basis of reciprocal interactions between Mo_AMs and fibroblasts through the activation of the ERK pathway in Mo_AMs. SPP1_RecMacs (RecMacs, recruited macrophages) were higher in the low-FVC group than in the high-FVC group. Specifically, compared with TRMs, the functions of lipid and energetic metabolism as well as tissue repair were higher in Mo_AMs than TRMs. But, TRMs may have higher level of phagocytosis than TRMs. SPIB (PU.1), JUNB, JUND, BACH2, FOSL2, and SMARCC1 showed stronger association with open chromatin of Mo_AMs than TRMs. Significant upregulated expression and deep chromatin accessibility of APOE were observed in both SPP1_RecMacs and TRMs. Conclusion Through trajectory analysis, it was confirmed that SPP1_RecMacs derived from Monocytes. Besides, Mo_AMs may influence FVC% pred and aggravate pulmonary fibrosis through the communication with fibroblasts. Furthermore, distinctive transcriptional regulators between Mo_AMs and TRMs implied that they may depend on different upstream regulatory mechanisms. Overall, this work provides a global overview of how Mo_AMs govern IPF and also helps determine better approaches and intervention therapies.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1479-5876
DOI: 10.1186/s12967-024-05398-y
DOI: 10.21203/rs.3.rs-3883875/v1
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38937806
https://doaj.org/article/c5f5488bceb24197a6340d4916cc48b8
https://repository.publisso.de/resource/frl:6502874
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (http://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Prístupové číslo: edsair.doi.dedup.....843c91301635434f8acbb5c99a1024e4
Databáza: OpenAIRE
Popis
Abstrakt:Background Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq analysis has proven valuable in the transcriptome profiling of Mo_AMs, the integration analysis of multi-omics may provide additional dimensions of understanding of these cellular populations. Methods We performed multi-omics analysis on 116 scRNAseq, 119 bulkseq and five scATACseq lung tissue samples from IPF. We built a large-scale IPF scRNAseq atlas and conducted the Monocle 2/3 as well as the Cellchat to explore the developmental path and intercellular communication on Mo_AMs. We also reported the difference in metabolisms, tissue repair and phagocytosis between Mo_AMs and tissue-resident alveolar macrophages (TRMs). To determine whether Mo_AMs affected pulmonary function, we projected clinical phenotypes (FVC%pred) from the bulkseq dataset onto the scRNAseq atlas. Finally, we used scATATCseq to uncover the upstream regulatory mechanisms and determine key drivers in Mo_AMs. Results We identified three Mo_AMs clusters and the trajectory analysis further validated the origin of these clusters. Moreover, via the Cellchat analysis, the CXCL12/CXCR4 axis was found to be involved in the molecular basis of reciprocal interactions between Mo_AMs and fibroblasts through the activation of the ERK pathway in Mo_AMs. SPP1_RecMacs (RecMacs, recruited macrophages) were higher in the low-FVC group than in the high-FVC group. Specifically, compared with TRMs, the functions of lipid and energetic metabolism as well as tissue repair were higher in Mo_AMs than TRMs. But, TRMs may have higher level of phagocytosis than TRMs. SPIB (PU.1), JUNB, JUND, BACH2, FOSL2, and SMARCC1 showed stronger association with open chromatin of Mo_AMs than TRMs. Significant upregulated expression and deep chromatin accessibility of APOE were observed in both SPP1_RecMacs and TRMs. Conclusion Through trajectory analysis, it was confirmed that SPP1_RecMacs derived from Monocytes. Besides, Mo_AMs may influence FVC% pred and aggravate pulmonary fibrosis through the communication with fibroblasts. Furthermore, distinctive transcriptional regulators between Mo_AMs and TRMs implied that they may depend on different upstream regulatory mechanisms. Overall, this work provides a global overview of how Mo_AMs govern IPF and also helps determine better approaches and intervention therapies.
ISSN:14795876
DOI:10.1186/s12967-024-05398-y