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

First Author  Wu Y Year  2023
Journal  iScience Volume  26
Issue  7 Pages  107197
PubMed ID  37456831 Mgi Jnum  J:359988
Mgi Id  MGI:7510757 Doi  10.1016/j.isci.2023.107197
Citation  Wu Y, et al. (2023) Single cell RNA sequencing unravels mechanisms underlying senescence-like phenotypes of alveolar macrophages. iScience 26(7):107197
abstractText  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 CBFbeta 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 CBFbeta 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 beta activity.
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