Cellular Quiescence Displays a Transcriptional Inflammatory Phenotype Similar to the One in Cellular Senescence [scRNA-seq]

Cellular senescence, traditionally viewed as the irreversible arrest of proliferating cells in response to stress and DNA damage, is a key mechanism underlying cellular aging. Several studies have identified a process called ”quiescence-origin senescence,” where quiescent cells bypass proliferation and transition directly into senescence. In this context, we introduce the concept of the transcriptional Quiescence-Associated Secretory Phenotype (tQASP), a putative inflammatory secretory profile that arises in human quiescent cells and may serve as a precursor to the full senescence-associated secretory phenotype (SASP). We report that quiescent cells express tQASP genes in a cell-type-, induction-dependent manner and that this response is influenced by environmental oxygen levels. tQASP expression is also increased in tissue affected by Idiopathic Pulmonary Fibrosis (IPF) and shows a positive correlation with myofibroblast activation. Together, these data support the concept of a continuum between quiescence and senescence and suggest that the tQASP may be an early marker of cellular aging, with significant implications for tissue homeostasis, aging, cancer, and disease progression. Overall design: single cell RNA Sequencing of quiescent human Lung fibroblasts (LF1) induced by a combination of contact inhibition and serum withdrawal