RT Journal Article
SR Electronic
T1 Cell-type-specific nucleotide sharing through gap junctions impacts sensitivity to replication stress
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.08.15.553366
DO 10.1101/2023.08.15.553366
A1 Boumard, Benjamin
A1 Meur, Gwenn Le
A1 Stefanutti, Marine
A1 Maalouf, Tania
A1 El-Hajj, Marwa
A1 Bauer, Reinhard
A1 Bardin, Allison J.
YR 2024
UL http://biorxiv.org/content/early/2024/09/17/2023.08.15.553366.abstract
AB Cell proliferation underlying tissue growth and homeostasis, requires high levels of metabolites such as deoxynucleotides (dNTPs). The dNTP pool is known to be tightly cell-autonomously regulated via de novo synthesis and salvage pathways. Here, we reveal that nucleotides can also be provided to cells non-autonomously by surrounding cells within a tissue. Using Drosophila epithelial tissues as models, we find that adult intestinal stem cells are highly sensitive to nucleotide depletion whereas wing progenitor cells are not. Wing progenitor cells share nucleotides through gap junction connections, allowing buffering of replication stress induced by nucleotide pool depletion. Adult intestinal stem cells, however, lack gap junctions and cannot receive dNTPs from neighbors. Collectively, our data suggest that gap junction-dependent sharing between cells can contribute to dNTP pool homeostasis in vivo. We propose that inherent differences in cellular gap junction permeability can influence sensitivity to fluctuations of intracellular dNTP levels.One-Sentence Summary The nucleotide pool can be shared between adjacent cells through gap junctions allowing tissue-level buffering of replication stress.Competing Interest StatementThe authors have declared no competing interest.