A phenopushing platform to identify compounds that alleviate acute hypoxic stress by fast-tracking cellular adaptation.

ABSTRACT: Severe acute hypoxic stress is a major contributor to the pathology of human diseases, including ischemic disorders. Current treatments focus on managing consequences of hypoxia, with few addressing cellular adaptation to low-oxygen environments. Here, we investigate whether accelerating hypoxia adaptation could provide a strategy to alleviate acute hypoxic stress. We develop a high-content phenotypic screening platform to identify compounds that fast-track adaptation to hypoxic stress. Our platform captures a high-dimensional phenotypic hypoxia response trajectory consisting of normoxic, acutely stressed, and chronically adapted cell states. Leveraging this trajectory, we identify compounds that phenotypically shift cells from the acutely stressed state towards the adapted state, revealin

SUBMITTER: Li L 

PROVIDER: S-EPMC11920246 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature