Features and mechanism investigation of long-lived myotis somatic fibroblasts in response to DNA replication stress

DNA replication stress (RS) response is crucial for cellular homeostasis and physiological longevity. However, the characters and core mechanisms in long-lived species such as bats in regulating RS to maintain genomic stability remain unclear. Also, the moonlighting functions of ribosome factors in genomic stabilization are observed recently. In this study, we utilized the somatic skin fibroblasts from long-lived big-footed bat (Myotis pilosus) as an in vitro cultured model, and found bat cells exhibit stronger tolerance to RS compared to mouse cells. Through comparative transcriptome analysis, we observed significant differences in gene expression patterns between bat and mouse cells in response to RS, particularly a teeterboard model showing upregulation of ribosome biogenesis pathway. Meanwhile, the activation status of P53 signaling pathway in bat cells was much lower than mouse cells in response to RS. This emphasizes unique intrinsic homeostasis strategy in bat cells. In addition, we focused on Nufip1 gene, a ribosome associated factor highly expressed in bat cells, and identified the association between Nufip1 and Rps27l in order to be a cross linker of ribosome biogenesis and P53 signaling networks. In summary, this study provides direct cellular and molecular evidence for deep understanding of the biological characteristics and genomic maintenance mechanisms of long-lived bat species.