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Successful axonal regeneration is driven by evolutionarily conserved metabolic reprogramming

ABSTRACT: Successful axonal regeneration is driven by evolutionarily conserved metabolic reprogramming

PROVIDER: PRJNA1221797 | ENA |

REPOSITORIES: ENA

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Successful axonal regeneration is driven by evolutionarily conserved metabolic reprogramming

Project description:Unlike mammals, zebrafish can regrow axons after injury and restore circuit function in the central nervous system (CNS). Mitochondria have been identified as key players in this process, but how different metabolic pathways work together to sustain regeneration remains unclear. Using RNA sequencing of adult zebrafish retinal ganglion cells (RGCs) after optic nerve crush injury, we demonstrate that oxidative phosphorylation is downregulated during axonal regrowth. Simultaneously, the thioredoxin antioxidant system is upregulated, likely to limit oxidative damage. Additionally, we observe an integrated upregulation of glycolysis and the pentose phosphate pathway during the initial regrowth phases, possibly to provide energy while supplying NADPH for biosynthesis and antioxidant responses. We show that this metabolic reprogramming is evolutionarily conserved, as it also occurs in the pro-regenerative mammalian Pten and Socs3 co-deletion model. Inhibiting glycolysis and thioredoxin in zebrafish impairs axonal regrowth, suggesting that targeting these pathways could enhance CNS regeneration in mammals.

2025-02-15 | GSE289140 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.

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A transphyletic approach to analyzing evolutionarily conserved β-catenin modules

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2023-07-08 | PXD035167 | JPOST Repository

Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration.

Project description:BACKGROUND:Defining conserved molecular pathways in animal models of successful cardiac regeneration could yield insight into why adult mammals have inadequate cardiac regeneration after injury. Insight into the transcriptomic landscape of early cardiac regeneration from model organisms will shed light on evolutionarily conserved pathways in successful cardiac regeneration. METHODS:Here we describe a cross-species transcriptomic screen in 3 model organisms for cardiac regeneration: axolotl, neonatal mice, and zebrafish. Apical resection to remove ?10% to 20% of ventricular mass was carried out in these model organisms. RNA-sequencing analysis was performed on the hearts harvested at 3 time points: 12, 24, and 48 hours after resection. Sham surgery was used as internal control. RESULTS:Genes associated with inflammatory processes were found to be upregulated in a conserved manner. Complement receptors (activated by complement components, part of the innate immune system) were found to be highly upregulated in all 3 species. This approach revealed induction of gene expression for complement 5a receptor 1 in the regenerating hearts of zebrafish, axolotls, and mice. Inhibition of complement 5a receptor 1 significantly attenuated the cardiomyocyte proliferative response to heart injury in all 3 species. Furthermore, after left ventricular apical resection, the cardiomyocyte proliferative response was diminished in mice with genetic deletion of complement 5a receptor 1. CONCLUSIONS:These data reveal that activation of complement 5a receptor 1 mediates an evolutionarily conserved response that promotes cardiomyocyte proliferation after cardiac injury and identify complement pathway activation as a common pathway of successful heart regeneration.

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An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis

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Isoform-specific translational control is evolutionarily conserved in primates

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Identification of Evolutionarily Conserved VSX2 Enhancers in Retinal Development

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Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [ATAC-seq]

Project description:The lung alveolus is the primary site of gas exchange in mammals. Within the alveolus, the alveolar type 2 (AT2) epithelial cell population generates surfactant to maintain alveolar structure and harbors a regenerative capacity to repair the alveolus after injury. We show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the AT2 cell population is critical for regenerating the alveolar niche. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a majority of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome, and functional phenotype with specific responsiveness to Wnt and FGF signaling that modulates differentiation and self-renewal, respectively. Importantly, human AEPs (hAEPs) can be isolated and characterized through a conserved surface marker and are required for human alveolar self-renewal and differentiation using alveolar organoid assays. Together, our findings show that AEPs are an evolutionarily conserved alveolar progenitor lineage essential for regenerating the alveolar niche in the mammalian lung.

2018-01-08 | GSE97052 | GEO

RNA seq analysis of regenerating hearts from three models of successful cardiac regeneration

Project description:Defining conserved molecular pathways in animal models of successful cardiac regeneration could yield insight into why adult mammals have inadequate cardiac regeneration after injury. Here we describe a cross-species transcriptomic screen to identify evolutionarily conserved pathways in the early events of cardiac regeneration in three species that can regenerate myocardium after a major injury. In this study, we performed RNA-seq on regenerating hearts from three model organisms - axolotl, zebrafish and mouse. Apical resection was performed to amputate ~10 - 20% of the left ventricle in all three model organisms. Following resection, hearts were harvested at 12, 24 and 48 hours post-resection and subjected to RNA-seq. RNA-seq on sham controls (no ventricular amputation) was used as interanal control. This approach revealed upregulation of inflammatory genes in all three organisms during regeneration. Furthermore, upregulation of Complement 5a receptor1 (C5aR1) expression in the regenerating hearts of zebrafish, axolotls and mice was observed.

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Spatial proteogenomics reveals distinct and evolutionarily-conserved hepatic macrophage niches

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