Faculty Collaboration Database

Death-seq identifies regulators of cell death and senolytic therapies. Cell Metab 2023 Oct 03;35(10):1814-1829.e6

Date

09/13/2023

Pubmed ID

37699398

Pubmed Central ID

PMC10597643

DOI

10.1016/j.cmet.2023.08.008

Scopus ID

2-s2.0-85172695750 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Selectively ablating damaged cells is an evolving therapeutic approach for age-related disease. Current methods for genome-wide screens to identify genes whose deletion might promote the death of damaged or senescent cells are generally underpowered because of the short timescales of cell death as well as the difficulty of scaling non-dividing cells. Here, we establish "Death-seq," a positive-selection CRISPR screen optimized to identify enhancers and mechanisms of cell death. Our screens identified synergistic enhancers of cell death induced by the known senolytic ABT-263. The screen also identified inducers of cell death and senescent cell clearance in models of age-related diseases by a related compound, ABT-199, which alone is not senolytic but exhibits less toxicity than ABT-263. Death-seq enables the systematic screening of cell death pathways to uncover molecular mechanisms of regulated cell death subroutines and identifies drug targets for the treatment of diverse pathological states such as senescence, cancer, and fibrosis.

Author List

Colville A, Liu JY, Rodriguez-Mateo C, Thomas S, Ishak HD, Zhou R, Klein JDD, Morgens DW, Goshayeshi A, Salvi JS, Yao D, Spees K, Dixon SJ, Liu C, Rhee JW, Lai C, Wu JC, Bassik MC, Rando TA

Author

Chun Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aniline Compounds
Cell Death
Cellular Senescence