Epigenetic Regulation of Organ Regeneration in Zebrafish

Zhu, Xiaojun; Xiao, Chenglu; Xiong, Jing-Wei

doi:10.3390/jcdd5040057

Cited by 14 publications

(18 citation statements)

References 95 publications

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“…Epigenetic mechanisms associated with regeneration have been partially investigated in organisms that have the capability to regenerate their tissues after injury [28][29][30][31][32][33]. For example, in the Xenopus froglet, DNA methylation affects the limb regenerative capacity mediated by an enhancer sequence named Mammalian Fish Conserved Sequence 1 (MFCS1) which controls the expression of Shh [34].…”

Section: Introductionmentioning

confidence: 99%

DNA demethylation is a driver for chick retina regeneration

et al. 2020

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Cellular reprogramming resets the epigenetic landscape to drive shifts in transcriptional programmes and cell identity. The embryonic chick can regenerate a complete neural retina, after retinectomy, via retinal pigment epithelium (RPE) reprogramming in the presence of FGF2. In this study, we systematically analysed the reprogramming competent chick RPE prior to injury, and during different stages of reprogramming. In addition to changes in the expression of genes associated with epigenetic modifications during RPE reprogramming, we observed dynamic changes in histone marks associated with bivalent chromatin (H3K27me3/H3K4me3) and intermediates of the process of DNA demethylation including 5hmC and 5caC. Comprehensive analysis of the methylome by whole-genome bisulphite sequencing (WGBS) confirmed extensive rearrangements of DNA methylation patterns including differentially methylated regions (DMRs) found at promoters of genes associated with chromatin organization and fibroblast growth factor production. We also identified Tet methylcytosine dioxygenase 3 (TET3) as an important factor for DNA demethylation and retina regeneration, capable of reprogramming RPE in the absence of exogenous FGF2. In conclusion, we demonstrate that injury early in RPE reprogramming triggers genome-wide dynamic changes in chromatin, including bivalent chromatin and DNA methylation. In the presence of FGF2, these dynamic modifications are further sustained in the commitment to form a new retina. Our findings reveal active DNA demethylation as an important process that may be applied to remove the epigenetic barriers in order to regenerate retina in mammals.

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Section: Introductionmentioning

confidence: 99%

DNA demethylation is a driver for chick retina regeneration

et al. 2020

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“…Recent regenerative studies have predominately focussed on gene regulation and its post‐translational modification by utilizing a variety of genetic and epigenetic approaches, including genome and transcriptome sequencing, CRISPR‐Cas9, RNAi and chromatin immunoprecipitation‐sequencing (ChIP‐seq) 157‐159 . Following injury or amputation, the expression patterns of hundreds or even thousands of genes are thought to be altered intricately 2 .…”

Section: The Genetic Basis Of Crayfish Tissue Regenerationmentioning

confidence: 99%

“…Prod1 has a functional role in the directional growth of the limb during regeneration 160 . Emerging evidence strongly suggests epigenetic modifications exist in the crustacean genome, of which might be integral for successful tissue regeneration 159 . Examples of epigenetic processes include DNA methylation, histone chemical modification, non‐coding RNA, chromatin remodelling complexes and microRNAs 159 .…”

Section: The Genetic Basis Of Crayfish Tissue Regenerationmentioning

confidence: 99%

“…Emerging evidence strongly suggests epigenetic modifications exist in the crustacean genome, of which might be integral for successful tissue regeneration 159 . Examples of epigenetic processes include DNA methylation, histone chemical modification, non‐coding RNA, chromatin remodelling complexes and microRNAs 159 . In crustacea, the genome of Daphnia pulex , a freshwater crustacean was sequenced, rigorously analysed, and it appears that the modification, 5‐methyl‐cytosine (5‐mC) and 5‐hydroxymethyl‐cytosine (5‐hmc), is present in its DNA, implicating epigenetic regulation 161 .…”

Section: The Genetic Basis Of Crayfish Tissue Regenerationmentioning

confidence: 99%

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Biological insights into the rapid tissue regeneration of freshwater crayfish and crustaceans

Feleke

Bennett

Chen

et al. 2021

Cell Biochemistry & Function

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The freshwater crayfish is capable of regenerating limbs, following autotomy, injury and predation. In arthropod species, regeneration and moulting are two processes linked and strongly regulated by ecdysone. The regeneration of crayfish limbs is divided into wound healing, blastema formation, cellular reprogramming and tissue patterning. Limb blastema cells undergo proliferation, dedifferentiation and redifferentiation. A limb bud, containing folded segments of the regenerating limb, is encased within a cuticular sheath. The functional limb regenerates, in proecdysis, in two to three consecutive moults. Rapid tissue growth is regulated by hormones, limb nerves and local cells. The TGF‐β/activin signalling pathway has been determined in the crayfish, P. fallax f. virginalis, and is suggested as a potential regulator of tissue regeneration. In this review article, we discuss current understanding of tissue regeneration in the crayfish and various crustaceans. A thorough understanding of the cellular, genetic and molecular pathways of these biological processes is promising for the development of therapeutic applications for a wide array of diseases in regenerative medicine.

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“…Additionally, this approach may reveal injury-specific regulatory sequences. Such information is very valuable, since injury-active regions can be deleted and prevent the activation of genes upon injury and not during development, overcoming possible genomic compensation (Zhu et al, 2018).…”

Section: Conclusion Of Cis-regulatory Elements Studymentioning

confidence: 99%

Study of Midkine-a and Caveolin-1 in zebrafish heart regeneration

Grivas¹

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Zebrafish have the ability to regenerate cardiac tissue after injury in contrast to mammals.Cryoinjury of the heart triggers a regenerative program that includes inflammatory response, cell proliferation and formation of a transient scar that eventually lead to complete tissue regeneration. This thesis focused on understanding the molecular and mechanical properties governing zebrafish heart regeneration. In particular, we studied the role of midkine-a (mdka) and caveolin-1 (cav1), two genes that were upregulated in a microarray analysis of regenerating hearts performed in the laboratory. Additionally, we studied the epigenetic regulation of mdka and tested in vivo different mdka cis-regulatory elements with the goal to identify the minimum regulatory regions that drive mdka expression in development and after injury.Midkine-a (Mdka) is a neurite-growth factor that is involved in the formation of the media floor plate in zebrafish. Here, we show that mdka expression was strongly induced after heart injury, although it was not expressed in intact hearts. In injured hearts, the onset of mdka expression was one-day post cryoinjury (dpci) in all the epicardial layer, whereas by 7dpci the expression became restricted to the epicardial cells covering the injured area. To study the role of Mdka in heart regeneration, we generated mdka-knock out (KO) zebrafish strains. In injured heart, mdka depletion did not trigger upregulation of mdkb and ptn, the two other members of the midkine gene family, which might compensate for the loss of Mdka. Analysis of 90dpci hearts showed that mdka deletion resulted in impaired heart regeneration, with the injured area enriched in collagen deposition.However, the proliferation ratio of cardiomyocytes (CM) and epicardial cells was not affected.Analysis of extracellular matrix turnover, immune cells infiltration in the injured area and revascularization of the regenerating tissue will clarify the reasons for the impaired cardiac regeneration in mdka-KO hearts.During development, mdka is expressed in neural tissues such us neural tube and brain, and is not detected neither in developing hearts nor in adult intact hearts. However, mdka expression was activated upon heart injury, having dynamic expression pattern. To investigate such a change in the expression pattern, we used available ChIP-seq and ATAC-seq data to analyse the epigenetic landscape of mdka. In mdka locus, there are three intronic enhancer sequences and two additional enhancers located upstream of mdka. We tested these enhancers and the mdka promoter linked to GFP reporter and studied their expression patterns in our transgenic lines. We found that the promoter of mdka and the intronic enhancers were responsible for the spatio-temporal expression pattern of mdka during development, in adult tissues and after injury of the heart and the fin.Caveolin-1 (Cav1) is the structural protein of caveolae, small membrane invaginations that are involved in signal transduction and mechanoprotection. Our expression analysis showed that Cav1...

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Epigenetic Regulation of Organ Regeneration in Zebrafish

Cited by 14 publications

References 95 publications

DNA demethylation is a driver for chick retina regeneration

DNA demethylation is a driver for chick retina regeneration

Biological insights into the rapid tissue regeneration of freshwater crayfish and crustaceans

Study of Midkine-a and Caveolin-1 in zebrafish heart regeneration

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