PUBLICATION
Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration
- Authors
- Linsley, J.W., Shah, K., Castello, N., Chan, M., Haddad, D., Doric, Z., Wang, S., Leks, W., Mancini, J., Oza, V., Javaherian, A., Nakamura, K., Kokel, D., Finkbeiner, S.
- ID
- ZDB-PUB-210908-3
- Date
- 2021
- Source
- Nature communications 12: 5284 (Journal)
- Registered Authors
- Finkbeiner, Steve
- Keywords
- none
- MeSH Terms
-
- Primary Cell Culture
- Embryo, Nonmammalian
- Humans
- Cell Death/genetics*
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Rats, Long-Evans
- Neurodegenerative Diseases/genetics*
- Neurodegenerative Diseases/metabolism
- Neurodegenerative Diseases/pathology
- Mice, Inbred C57BL
- Mice
- alpha-Synuclein/genetics
- alpha-Synuclein/metabolism
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Neurons/cytology
- Neurons/drug effects
- Neurons/metabolism*
- Fluorescent Dyes/chemistry
- Cerebral Cortex/cytology
- Cerebral Cortex/metabolism
- Larva/cytology
- Larva/genetics
- Larva/growth & development
- Larva/metabolism
- Superoxide Dismutase-1/genetics
- Superoxide Dismutase-1/metabolism
- Rats
- Single-Cell Analysis/methods
- Disease Models, Animal
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Biosensing Techniques*
- Gene Expression Regulation, Developmental*
- Genes, Reporter
- Glutamic Acid/pharmacology
- Calcium/metabolism
- Animals
- PubMed
- 34489414 Full text @ Nat. Commun.
Citation
Linsley, J.W., Shah, K., Castello, N., Chan, M., Haddad, D., Doric, Z., Wang, S., Leks, W., Mancini, J., Oza, V., Javaherian, A., Nakamura, K., Kokel, D., Finkbeiner, S. (2021) Genetically encoded cell-death indicators (GEDI) to detect an early irreversible commitment to neurodegeneration. Nature communications. 12:5284.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping