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Yue Wu, Bibo Zhu, Ruixuan Zhang, Zheng Wang, Nick P Goplen, Xiaochen Gao, Ying Li, Amber Cadani, Thomas J Braciale, Jie Sun, Zom-biecoming: Single-Cell RNA-seq reveals senescence-like features of alveolar macrophages during aging, The Journal of Immunology, Volume 206, Issue 1_Supplement, May 2021, Page 55.06, https://doi.org/10.4049/jimmunol.206.Supp.55.06
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Abstract
Alveolar Macrophages (AMs) are unique innate immune cells that reside in the alveolar space and accommodate the ever-changing need of the lungs against internal and external challenges. During homeostasis, AMs maintained themselves through self-renewal without the need for the input of adult hematopoietic stem cells. Currently, little is known about how aging influences AM dynamics, heterogeneity and transcriptional profiles. Here, we identified the transcription factor, Cbfb, has indispensable role in AM self-renew ability. In the bone marrow chimera mice with genetic knock-out of Cbfb specifically in the myeloid compartment, AMs displayed reduced proliferation and an immature phenotype. Moreover, with the analysis of the combined scRNA-seq data of the FACS sorted AMs (CD11+ Siglec F+) in young(~8w) and aged(~2y) mice, we discovered that despite for the similar transcriptome in the proliferating cells, the AMs from the aged mice had reduced embryotic-stem cell (ESC)-like features. The AMs from the aged host also had reduced DNA repair ability, which could contribute to their impaired capacity to pass through the cell cycle checkpoints and elevation of senescence markers. In accordance with the analysis, we observed reduced number of AMs in the aged mice, which had abrogated self-renew ability and were more sensitive to the reduction of GM-CSF. Increased b-galactosidase staining was also observed in the AMs from the aged mice. Taken together, we concluded that AMs in the aged host harbor a senescence-like phenotype. Further investigation is warranted for the mechanism and pathophysiological consequences of the accumulation of AMs with senescence-like phenotype in the aged host.
