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Non‐apoptotic caspase activation preserves Drosophila intestinal progenitor cells in quiescence
Author(s) -
Arthurton Lewis,
Nahotko Dominik Antoni,
Alonso Jana,
Wendler Franz,
BaenaLopez Luis Alberto
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948892
Subject(s) - biology , microbiology and biotechnology , progenitor cell , caspase , stem cell , apoptosis , progenitor , caspase 8 , caspase 2 , enterocyte , programmed cell death , genetics , biochemistry , small intestine
Caspase malfunction in stem cells often precedes the appearance and progression of multiple types of cancer, including human colorectal cancer. However, the caspase‐dependent regulation of intestinal stem cell properties remains poorly understood. Here, we demonstrate that Dronc , the Drosophila ortholog of caspase‐ 9/2 in mammals, limits the number of intestinal progenitor cells and their entry into the enterocyte differentiation programme. Strikingly, these unexpected roles for Dronc are non‐apoptotic and have been uncovered under experimental conditions without epithelial replenishment. Supporting the non‐apoptotic nature of these functions, we show that they require the enzymatic activity of Dronc, but are largely independent of the apoptotic pathway. Alternatively, our genetic and functional data suggest that they are linked to the caspase‐mediated regulation of Notch signalling. Our findings provide novel insights into the non‐apoptotic, caspase‐dependent modulation of stem cell properties that could improve our understanding of the origin of intestinal malignancies.