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Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy

View ORCID ProfileAlessia Galasso, Daria Iakovleva, View ORCID ProfileLuis Alberto Baena-Lopez
doi: https://doi.org/10.1101/722330
Alessia Galasso
1Sir William Dunn School of Pathology. University of Oxford. South Parks Road. Oxfordshire, UK. OX1 3RE
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Daria Iakovleva
2Center for Regenerative Medicine. University of Edinburgh. 5 Little France Dr, Edinburgh EH16 4UU
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Luis Alberto Baena-Lopez
1Sir William Dunn School of Pathology. University of Oxford. South Parks Road. Oxfordshire, UK. OX1 3RE
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  • For correspondence: alberto.baenalopez@path.ox.ac.uk
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ABSTRACT

There is increasing evidence associating the activity of caspases with the regulation of basic cellular functions beyond apoptosis. Accordingly, the dysregulation of these novel non-apoptotic functions often sits at the origin of neurological disorders, metabolic defects, autoimmunity, and cancer. However, the molecular interplay between caspases and the signalling networks active in non-apoptotic cellular scenarios remains largely unknown. Our work show that non-apoptotic caspase activation is critical to modulate Hedgehog-signalling and autophagy in ovarian somatic cells from both Drosophila and humans under moderate stress. We also demonstrate that these novel caspase functions are key to sustain stem cell proliferation and differentiation without inducing apoptosis. Finally, we molecularly link these caspase-dependent effects to the fine-tuning of the Hedgehog-receptor, Patched. Together, these findings confer a pro-survival role to the caspases, as opposed to the widely held apoptotic function assigned to these enzymes.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • This version of the manuscript contains additional experiments, improved figures and data analyses.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 27, 2020.
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Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy
Alessia Galasso, Daria Iakovleva, Luis Alberto Baena-Lopez
bioRxiv 722330; doi: https://doi.org/10.1101/722330
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Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy
Alessia Galasso, Daria Iakovleva, Luis Alberto Baena-Lopez
bioRxiv 722330; doi: https://doi.org/10.1101/722330

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