Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages

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

doi:10.1016/j.isci.2023.107197

Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages

iScience. 2023 Jun 23;26(7):107197. doi: 10.1016/j.isci.2023.107197. eCollection 2023 Jul 21.

Authors

Yue Wu^{1

2}, Shengen Shawn Hu³, Ruixuan Zhang^{4

5

6}, Nick P Goplen⁷, Xiaochen Gao^{1

2}, Harish Narasimhan^{5

6}, Ao Shi¹, Yin Chen^{1

2}, Ying Li⁸, Chongzhi Zang^{3

9

10}, Haidong Dong^{2

11}, Thomas J Braciale^{5

6}, Bibo Zhu^{4

5

6}, Jie Sun^{1

2

4

5

6}

Affiliations

¹ Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN 55905, USA.
² Mayo Clinic Department of Immunology, Rochester, MN 55905, USA.
³ Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
⁴ Division of Pulmonary and Critical Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
⁵ Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
⁶ Division of Infectious Disease and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
⁷ Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA.
⁸ Division of Computational Biology, Mayo Clinic, Rochester, MN 55905, USA.
⁹ Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA.
¹⁰ UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, VA 22908, USA.
¹¹ Department of Urology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

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.

Keywords: Bioinformatics; Omics; Transcriptomics.

Abstract

Grants and funding