A Metabolic Shift to Glycolysis Promotes Zebrafish Tail Regeneration Through TGF-β Dependent Dedifferentiation of Notochord Cells to Form the Blastema

Sinclair, Jason; Hoying, David R.; Bresciani, Erica; Nogare, Damian Dalle; Needle, Carli D.; Wu, Weiwei; Bishop, Kevin; Elkahloun, Abdel G.; Chitnis, Ajay B.; Liu, Paul

doi:10.2139/ssrn.3548262

Cited by 2 publications

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“…Indeed, our RNA-Seq data suggest that transcription of regulators of amino acid metabolism, glycolysis, the tricarboxylic acid cycle, and other metabolic pathways respond to apob(RNAi) , suggesting that planarian stem cell metabolism is just as dynamic as in other animals. The fact that apob(RNAi) seems to primarily affect post-mitotic states also suggests that planarian neoblasts might rely primarily on glycolysis for energy, and shift to lipid metabolism and oxidative phosphorylation during differentiation, as in other systems (Shyh-Chang et al, 2013; Love et al, 2014; Sinclair et al, 2020). Again, studies in animals with high regenerative capacity could generate greater insights into whether and how injury can induce metabolic switching.…”

Section: Discussionmentioning

confidence: 99%

Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians

Wong

Cejda

et al. 2021

Preprint

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Little is known about how lipid mobilization and utilization are modulated during stem-cell-driven tissue growth during regeneration. Planarian flatworms can regenerate all missing tissues in 10 days due to the proliferation and differentiation of pluripotent somatic stem cells called neoblasts. In planarians, diet-derived neutral lipids are stored in the intestine. Here, we identify two intestine-enriched paralogs of apolipoprotein b, apob-1 and apob-2, that are required for regeneration. Consistent with apolipoproteins' known roles regulating neutral lipid (NL) transport in lipoprotein particles (LPs), NLs increased in the intestine upon simultaneous dsRNA-mediated knockdown of apob-1 and apob-2, but were depleted in neoblasts and their progeny. apob knockdown reduced regeneration blastema morphogenesis, and delayed re-establishment of axial polarity and regeneration of multiple organs. Using flow cytometry, we found that neoblast progeny accumulated in apob(RNAi) animals, with minimal effects on neoblast maintenance or proliferation. In addition, ApoB reduction primarily dysregulated expression of transcripts enriched in neoblast progeny and mature cell types, compared to cycling neoblasts. Together, our results provide evidence that intestine-derived lipids serve as a source of metabolites required for neoblast differentiation. In addition, these findings demonstrate that planarians are a tractable model for elucidating specialized mechanisms by which lipid metabolism must be regulated during animal regeneration.

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Section: Discussionmentioning

confidence: 99%