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Metabolic reprogramming and membrane glycan remodeling as potential drivers of zebrafish heart regeneration.

Renza SpelatFederico FerroPaolo ContessottoAmal AljaabarySergio Martín-SaldañaChunsheng JinNiclas G KarlssonMaura GrealyMarkus M HilscherFulvio MagniClizia ChinelloMichelle KilcoyneAbhay Pandit
Published in: Communications biology (2022)
The ability of the zebrafish heart to regenerate following injury makes it a valuable model to deduce why this capability in mammals is limited to early neonatal stages. Although metabolic reprogramming and glycosylation remodeling have emerged as key aspects in many biological processes, how they may trigger a cardiac regenerative response in zebrafish is still a crucial question. Here, by using an up-to-date panel of transcriptomic, proteomic and glycomic approaches, we identify a metabolic switch from mitochondrial oxidative phosphorylation to glycolysis associated with membrane glycosylation remodeling during heart regeneration. Importantly, we establish the N- and O-linked glycan structural repertoire of the regenerating zebrafish heart, and link alterations in both sialylation and high mannose structures across the phases of regeneration. Our results show that metabolic reprogramming and glycan structural remodeling are potential drivers of tissue regeneration after cardiac injury, providing the biological rationale to develop novel therapeutics to elicit heart regeneration in mammals.
Keyphrases
  • stem cells
  • heart failure
  • atrial fibrillation
  • left ventricular
  • wound healing
  • clinical trial
  • cell surface
  • small molecule
  • high resolution
  • climate change
  • mass spectrometry
  • rna seq
  • label free