Journal article
SLAM-ITseq identifies that Nrf2 induces liver regeneration through the pentose phosphate pathway
VWT Tan, TM Salmi, AP Karamalakis, A Gillespie, AJS Ong, JJ Balic, YC Chan, CE Bladen, KK Brown, MA Dawson, AG Cox
Developmental Cell | CELL PRESS | Published : 2024
Open access
Abstract
The liver exhibits a remarkable capacity to regenerate following injury. Despite this unique attribute, toxic injury is a leading cause of liver failure. The temporal processes by which the liver senses injury and initiates regeneration remain unclear. Here, we developed a transgenic zebrafish model wherein hepatocyte-specific expression of uracil phosphoribosyltransferase (UPRT) enabled the implementation of SLAM-ITseq to investigate the nascent transcriptome during initiation of liver injury and regeneration. Using this approach, we identified a rapid metabolic transition from the fed to the fasted state that was followed by induction of the nuclear erythroid 2-related factor (Nrf2) antiox..
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Grants
Awarded by Cancer Council Victoria
Funding Acknowledgements
We thank the staff from the following facilities for their support: Molecular Genomics Core (Peter MacCallum Cancer Centre) , the Flow Cytometry Facility (Peter MacCallum Cancer Centre) , Centre for Advanced Histology & Microscopy (Peter MacCallum Cancer Centre) , and the DrUM Zebrafish Core Facility (University of Melbourne) . We thank the following funders for fellowship, scholarship, and grant support: Sir Edward Dunlop Fellowship, Cancer Council of Victoria, NHMRC Investigator Grant 1196749, and Howard Hughes Medical Institute International Research Scholarship 55008729 (M.A.D.) ; NHMRC Project Grant 1146558, NHMRC Investigator Grant GNT1176650, ARC Discovery Project Grant DP200102693, and Peter MacCallum Cancer Foundation (A.G.C.) ; Peter MacCallum Postgraduate Scholarship (V.W.T.T.) ; Yayasan Dayadiri Scholarship and Melbourne Research Scholarship (T.M.S.) ; Maddie Riewoldt's Vision 064728 (Y.-C.C.) ; and Melbourne Research Scholarship (C.E.B.) . The funders had no role in study design, data collection analysis, or decision to publish or preparation of the manuscript. Lastly, we extend our gratitude to members of the Cox, M. Dawson, Brown, Wickramasinghe, and S.J. Dawson Laboratories (Peter MacCallum Cancer Centre) for their helpful discussions.