Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration

Jeremy W. Linsley, Kevan Shah, Nicholas Castello, Michelle Chan, Dominik Haddad, Zak Doric, Shijie Wang, Wiktoria Leks, Jay Mancini, Viral Oza, Ashkan Javaherian, Ken Nakamura, David Kokel and Steven Finkbeiner ()
Additional contact information
Jeremy W. Linsley: Gladstone Center for Systems and Therapeutics
Kevan Shah: Gladstone Center for Systems and Therapeutics
Nicholas Castello: Gladstone Center for Systems and Therapeutics
Michelle Chan: Gladstone Center for Systems and Therapeutics
Dominik Haddad: Gladstone Institute of Neurologic Disease
Zak Doric: Gladstone Institute of Neurologic Disease
Shijie Wang: Gladstone Center for Systems and Therapeutics
Wiktoria Leks: Gladstone Center for Systems and Therapeutics
Jay Mancini: Gladstone Center for Systems and Therapeutics
Viral Oza: Gladstone Center for Systems and Therapeutics
Ashkan Javaherian: Gladstone Center for Systems and Therapeutics
Ken Nakamura: Gladstone Institute of Neurologic Disease
David Kokel: University of California
Steven Finkbeiner: Gladstone Center for Systems and Therapeutics

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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 family of fluorescent biosensors called genetically encoded death indicators (GEDIs). GEDIs specifically detect an intracellular Ca2+ level that cells achieve early in the cell death process and that marks a stage at which cells are irreversibly committed to die. The time-resolved nature of a GEDI delineates a binary demarcation of cell life and death in real time, reformulating the definition of cell death. We demonstrate that GEDIs acutely and accurately report death of rodent and human neurons in vitro, and show that GEDIs enable an automated imaging platform for single cell detection of neuronal death in vivo in zebrafish larvae. With a quantitative pseudo-ratiometric signal, GEDIs facilitate 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25549-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25549-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25549-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().