Short-term memory of past caspase activity biases cell elimination in vivo.
4 affiliations
- 1Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Cell Death and Epithelial Homeostasis Unit, Paris, France.
- 2Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
- 3Institut Pasteur, Université Paris Cité, Bioinformatics and Biostatistics Hub, Paris, France.
- 4Institut Pasteur, Université Paris Cité, CNRS UMR 3738, Cell Death and Epithelial Homeostasis Unit, Paris, France. [email protected].
Abstract
Apoptosis is triggered by the activation of Caspases leading to irreversible engagement in cell death. However, recent data outline numerous non-apoptotic functions of caspases as well as quite ubiquitous sublethal activation of effector caspases in vivo, opening the question of what drives the bifurcation between cell death and survival. Using quantitative live imaging combined with machine learning and optogenetics in the Drosophila pupal notum (a single-layer epithelium), we reveal the existence of a large heterogeneity of caspase activity thresholds between cells and distinct spatial domains with low or high sensitivity to caspases. We outline the central role of past exposure to sublethal caspase activity, which sensitises cells to apoptosis for several hours and reduces their threshold, and can bias single-cell elimination. Altogether, this work reveals the role of a cell's past history for apoptosis regulation in vivo, which can bias clonal selection and the spatial pattern of cell death.
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BibTeX
@article{cumming2026shortterm,
title = {{Short-term memory of past caspase activity biases cell elimination in vivo.}},
author = {Tom Cumming and Alexis Villars and Anđela Davidović and Florence Levillayer and Léo Valon and Romain Levayer},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77685-9},
url = {https://europepmc.org/article/MED/42907449},
note = {CC BY},
}
RIS
TY - JOUR
TI - Short-term memory of past caspase activity biases cell elimination in vivo.
AU - Tom Cumming
AU - Alexis Villars
AU - Anđela Davidović
AU - Florence Levillayer
AU - Léo Valon
AU - Romain Levayer
PY - 2026
DA - 2026/09/22
JO - Nature communications
DO - 10.1038/s41467-026-77685-9
UR - https://europepmc.org/article/MED/42907449
AB - Apoptosis is triggered by the activation of Caspases leading to irreversible engagement in cell death. However, recent data outline numerous non-apoptotic functions of caspases as well as quite ubiquitous sublethal activation of effector caspases in vivo, opening the question of what drives the bifurcation between cell death and survival. Using quantitative live imaging combined with machine learning and optogenetics in the Drosophila pupal notum (a single-layer epithelium), we reveal the existence of a large heterogeneity of caspase activity thresholds between cells and distinct spatial domains with low or high sensitivity to caspases. We outline the central role of past exposure to sublethal caspase activity, which sensitises cells to apoptosis for several hours and reduces their threshold, and can bias single-cell elimination. Altogether, this work reveals the role of a cell's past history for apoptosis regulation in vivo, which can bias clonal selection and the spatial pattern of cell death.
SN - 2041-1723
ER -