The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration

Abstract Throughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized a larval tail regeneration assay in the zebrafish Danio rerio, which serves as an ideal model of appendage regeneration due to its easy manipulation, relatively simple mixture...

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Autores principales:	Jason W. Sinclair, David R. Hoying, Erica Bresciani, Damian Dalle Nogare, Carli D. Needle, Alexandra Berger, Weiwei Wu, Kevin Bishop, Abdel G. Elkahloun, Ajay Chitnis, Paul Liu, Shawn M. Burgess
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/5119c383031f466eb2e13637fd267373
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spelling	oai:doaj.org-article:5119c383031f466eb2e13637fd2673732021-12-02T18:49:54ZThe Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration10.1038/s41536-021-00163-x2057-3995https://doaj.org/article/5119c383031f466eb2e13637fd2673732021-09-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00163-xhttps://doaj.org/toc/2057-3995Abstract Throughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized a larval tail regeneration assay in the zebrafish Danio rerio, which serves as an ideal model of appendage regeneration due to its easy manipulation, relatively simple mixture of cell types, and superior imaging properties. Regeneration of the embryonic zebrafish tail requires development of a blastema, a mass of dedifferentiated cells capable of replacing lost tissue, a crucial step in all known examples of appendage regeneration. Using this model, we show that tail amputation triggers an obligate metabolic shift to promote glucose metabolism during early regeneration similar to the Warburg effect observed in tumor forming cells. Inhibition of glucose metabolism did not affect the overall health of the embryo but completely blocked the tail from regenerating after amputation due to the failure to form a functional blastema. We performed a time series of single-cell RNA sequencing on regenerating tails with and without inhibition of glucose metabolism. We demonstrated that metabolic reprogramming is required for sustained TGF-β signaling and blocking glucose metabolism largely mimicked inhibition of TGF-β receptors, both resulting in an aberrant blastema. Finally, we showed using genetic ablation of three possible metabolic pathways for glucose, that metabolic reprogramming is required to provide glucose specifically to the hexosamine biosynthetic pathway while neither glycolysis nor the pentose phosphate pathway were necessary for regeneration.Jason W. SinclairDavid R. HoyingErica BrescianiDamian Dalle NogareCarli D. NeedleAlexandra BergerWeiwei WuKevin BishopAbdel G. ElkahlounAjay ChitnisPaul LiuShawn M. BurgessNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Jason W. Sinclair David R. Hoying Erica Bresciani Damian Dalle Nogare Carli D. Needle Alexandra Berger Weiwei Wu Kevin Bishop Abdel G. Elkahloun Ajay Chitnis Paul Liu Shawn M. Burgess The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
description	Abstract Throughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized a larval tail regeneration assay in the zebrafish Danio rerio, which serves as an ideal model of appendage regeneration due to its easy manipulation, relatively simple mixture of cell types, and superior imaging properties. Regeneration of the embryonic zebrafish tail requires development of a blastema, a mass of dedifferentiated cells capable of replacing lost tissue, a crucial step in all known examples of appendage regeneration. Using this model, we show that tail amputation triggers an obligate metabolic shift to promote glucose metabolism during early regeneration similar to the Warburg effect observed in tumor forming cells. Inhibition of glucose metabolism did not affect the overall health of the embryo but completely blocked the tail from regenerating after amputation due to the failure to form a functional blastema. We performed a time series of single-cell RNA sequencing on regenerating tails with and without inhibition of glucose metabolism. We demonstrated that metabolic reprogramming is required for sustained TGF-β signaling and blocking glucose metabolism largely mimicked inhibition of TGF-β receptors, both resulting in an aberrant blastema. Finally, we showed using genetic ablation of three possible metabolic pathways for glucose, that metabolic reprogramming is required to provide glucose specifically to the hexosamine biosynthetic pathway while neither glycolysis nor the pentose phosphate pathway were necessary for regeneration.
format	article
author	Jason W. Sinclair David R. Hoying Erica Bresciani Damian Dalle Nogare Carli D. Needle Alexandra Berger Weiwei Wu Kevin Bishop Abdel G. Elkahloun Ajay Chitnis Paul Liu Shawn M. Burgess
author_facet	Jason W. Sinclair David R. Hoying Erica Bresciani Damian Dalle Nogare Carli D. Needle Alexandra Berger Weiwei Wu Kevin Bishop Abdel G. Elkahloun Ajay Chitnis Paul Liu Shawn M. Burgess
author_sort	Jason W. Sinclair
title	The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
title_short	The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
title_full	The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
title_fullStr	The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
title_full_unstemmed	The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
title_sort	warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5119c383031f466eb2e13637fd267373
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The Warburg effect is necessary to promote glycosylation in the blastema during zebrafish tail regeneration

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