Abstract

BackgroundRegeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. We constructed four regenerative protein-protein interaction (PPI) networks using dynamic models and AIC (Akaike’s Information Criterion), based on time-course microarray data from the regeneration of four zebrafish organs: heart, cerebellum, fin, and retina. We extracted core and organ-specific proteins, and proposed a recalled-blastema-like formation model to uncover regeneration strategies in zebrafish.ResultsIt was observed that the core proteins were involved in TGF-β signaling for each step in the recalled-blastema-like formation model and TGF-β signaling may be vital for regeneration. Integrins, FGF, and PDGF accelerate hemostasis during heart injury, while Bdnf shields retinal neurons from secondary damage and augments survival during the injury response. Wnt signaling mediates the growth and differentiation of cerebellum and fin neural stem cells, potentially providing a signal to trigger differentiation.ConclusionThrough our analysis of all four zebrafish regenerative PPI networks, we provide insights that uncover the underlying strategies of zebrafish organ regeneration.

Highlights

  • Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses

  • The heart, cerebellum, fin, and retina time course microarray data sets were from Gene and Expression Omnibus (GEO) database of National Center of Biotechnology Information (NCBI) with accession number GSE56375 for cerebellum [8] with time points 0, 0.25, 1, and 3 days-post-injury, GSE37165 for fin [9] with time points 0, 0.5, 1, and 2 dpi, and GSE3303 for retina [8, 10] with time points 0, 2, 3, and 5 dpi

  • With the help of high-throughput data and systems biology methodology, we hope to unravel the fundamental mechanism of organ regeneration for zebrafish, which may lead to further breakthroughs in regenerative medicine

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Summary

Introduction

Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. The regenerative capacity of organs, such as the central nervous system (CNS, including cerebellum and cordial spinal), peripheral nervous system (PNS), heart, and limbs, is generally limited. This makes it difficult for mammals to recover from damages, such as heart defects and traumatic cerebellum injuries. The majority of the regenerating myocardium is believed to derive from resident Cmlc cardiomyocytes [5] These regeneration processes control similar biological functions, including assembling resident cells to act as the primary source of organ regeneration. This seems to indicate that a common regenerative mechanism may exist throughout different organs and tissues [1]

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