Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages
Summary: Alveolar macrophages (AMs) are resident innate immune cells that play vital roles in maintaining lung physiological functions. However, the effects of aging on their dynamics, heterogeneity, and transcriptional profiles remain to be fully elucidated. Through single cell RNA sequencing (scRN...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223012749 |
| _version_ | 1797774582666493952 |
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| author | Yue Wu Shengen Shawn Hu Ruixuan Zhang Nick P. Goplen Xiaochen Gao Harish Narasimhan Ao Shi Yin Chen Ying Li Chongzhi Zang Haidong Dong Thomas J. Braciale Bibo Zhu Jie Sun |
| author_facet | Yue Wu Shengen Shawn Hu Ruixuan Zhang Nick P. Goplen Xiaochen Gao Harish Narasimhan Ao Shi Yin Chen Ying Li Chongzhi Zang Haidong Dong Thomas J. Braciale Bibo Zhu Jie Sun |
| author_sort | Yue Wu |
| collection | DOAJ |
| description | Summary: Alveolar macrophages (AMs) are resident innate immune cells that play vital roles in maintaining lung physiological functions. However, the effects of aging on their dynamics, heterogeneity, and transcriptional profiles remain to be fully elucidated. Through single cell RNA sequencing (scRNA-seq), we identified CBFβ as an indispensable transcription factor that ensures AM self-renewal. Intriguingly, despite transcriptome similarities of proliferating cells, AMs from aged mice exhibited reduced embryonic stem cell–like features. Aged AMs also displayed compromised DNA repair abilities, potentially leading to obstructed cell cycle progression and an elevation of senescence markers. Consistently, AMs from aged mice exhibited impaired self-renewal ability and reduced sensitivity to GM-CSF. Decreased CBFβ was observed in the cytosol of AMs from aged mice. Similar senescence-like phenotypes were also found in human AMs. Taken together, these findings suggest that AMs in aged hosts demonstrate senescence-like phenotypes, potentially facilitated by the abrogated CBF β activity. |
| first_indexed | 2024-03-12T22:22:14Z |
| format | Article |
| id | doaj.art-ec17a509180142feabc6d01319d13f02 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:22:14Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ec17a509180142feabc6d01319d13f022023-07-23T04:55:54ZengElsevieriScience2589-00422023-07-01267107197Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophagesYue Wu0Shengen Shawn Hu1Ruixuan Zhang2Nick P. Goplen3Xiaochen Gao4Harish Narasimhan5Ao Shi6Yin Chen7Ying Li8Chongzhi Zang9Haidong Dong10Thomas J. Braciale11Bibo Zhu12Jie Sun13Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA; Mayo Clinic Department of Immunology, Rochester, MN 55905, USACenter for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USADivision of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA; Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USARobert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USAMayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA; Mayo Clinic Department of Immunology, Rochester, MN 55905, USACarter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USAMayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USAMayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA; Mayo Clinic Department of Immunology, Rochester, MN 55905, USADivision of Computational Biology, Mayo Clinic, Rochester, MN 55905, USACenter for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA; UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, VA 22908, USAMayo Clinic Department of Immunology, Rochester, MN 55905, USA; Department of Urology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USACarter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USADivision of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA; Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Corresponding authorMayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA; Mayo Clinic Department of Immunology, Rochester, MN 55905, USA; Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA; Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA; Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Corresponding authorSummary: Alveolar macrophages (AMs) are resident innate immune cells that play vital roles in maintaining lung physiological functions. However, the effects of aging on their dynamics, heterogeneity, and transcriptional profiles remain to be fully elucidated. Through single cell RNA sequencing (scRNA-seq), we identified CBFβ as an indispensable transcription factor that ensures AM self-renewal. Intriguingly, despite transcriptome similarities of proliferating cells, AMs from aged mice exhibited reduced embryonic stem cell–like features. Aged AMs also displayed compromised DNA repair abilities, potentially leading to obstructed cell cycle progression and an elevation of senescence markers. Consistently, AMs from aged mice exhibited impaired self-renewal ability and reduced sensitivity to GM-CSF. Decreased CBFβ was observed in the cytosol of AMs from aged mice. Similar senescence-like phenotypes were also found in human AMs. Taken together, these findings suggest that AMs in aged hosts demonstrate senescence-like phenotypes, potentially facilitated by the abrogated CBF β activity.http://www.sciencedirect.com/science/article/pii/S2589004223012749BioinformaticsOmicsTranscriptomics |
| spellingShingle | Yue Wu Shengen Shawn Hu Ruixuan Zhang Nick P. Goplen Xiaochen Gao Harish Narasimhan Ao Shi Yin Chen Ying Li Chongzhi Zang Haidong Dong Thomas J. Braciale Bibo Zhu Jie Sun Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages iScience Bioinformatics Omics Transcriptomics |
| title | Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages |
| title_full | Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages |
| title_fullStr | Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages |
| title_full_unstemmed | Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages |
| title_short | Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages |
| title_sort | single cell rna sequencing unravels mechanisms underlying senescence like phenotypes of alveolar macrophages |
| topic | Bioinformatics Omics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223012749 |
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