Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration
Jeremy W. Linsley, Kevan Shah, Nicholas Castello, Michelle Chan, Dominic Haddad, Jay Mancini, Viral Oza, Ashkan Javaherian, David Kokel, Steven Finkbeiner
Received Date: 18th December 19
Cell death is a critical process that occurs normally in health and disease. However, its study is limited due to available technologies that only detect very late stages in the process or specific death mechanisms. Here, we report the development of a new fluorescent biosensor called genetically encoded death indicator (GEDI). GEDI specifically detects an intracellular Ca2+ level that cells achieve early in the cell death process and marks a stage at which cells are irreversibly committed to die. The time-resolved nature of GEDI delineates a binary demarcation of cell life and death in real time, reformulating the definition of cell death. We demonstrate that GEDI acutely and accurately reports death of rodent and human neurons in vitro, and show GEDI enables a novel automated imaging platform for single cell detection of neuronal death in vivo in zebrafish larvae. With a quantitative pseudo-ratiometric signal, GEDI facilitates high-throughput analysis of cell death in time lapse imaging analysis, providing the necessary resolution and scale to identify early factors leading to cell death in studies of neurodegeneration.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.