PUBLICATION

Oct4 mediates Müller glia reprogramming and cell cycle exit during retina regeneration in zebrafish

Authors
Sharma, P., Gupta, S., Chaudhary, M., Mitra, S., Chawla, B., Khursheed, M.A., Ramachandran, R.
ID
ZDB-PUB-191011-13
Date
2019
Source
Life science alliance   2(5): (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Neuroglia/cytology
  • Neuroglia/physiology
  • MicroRNAs/metabolism
  • Zebrafish
  • Regeneration*
  • Gene Knockout Techniques
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • Gene Regulatory Networks
  • Retina/injuries*
  • Retina/physiology*
  • Octamer Transcription Factor-3/genetics
  • Octamer Transcription Factor-3/metabolism*
  • Cell Proliferation
  • Cellular Reprogramming
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Animals
  • Cell Cycle
(all 19)
PubMed
31594822 Full text @ Life Sci Alliance
Abstract
Octamer-binding transcription factor 4 (Oct4, also known as Pou5F3) is an essential pluripotency-inducing factor, governing a plethora of biological functions during cellular reprogramming. Retina regeneration in zebrafish involves reprogramming of Müller glia (MG) into a proliferating population of progenitors (MGPCs) with stem cell-like characteristics, along with up-regulation of pluripotency-inducing factors. However, the significance of Oct4 during retina regeneration remains elusive. In this study, we show an early panretinal induction of Oct4, which is essential for MG reprogramming through the regulation of several regeneration-associated factors such as Ascl1a, Lin28a, Sox2, Zeb, E-cadherin, and various miRNAs, namely, let-7a, miR-200a/miR-200b, and miR-143/miR-145 We also show the crucial roles played by Oct4 during cell cycle exit of MGPCs in collaboration with members of nucleosome remodeling and deacetylase complex such as Hdac1. Notably, Oct4 regulates Tgf-β signaling negatively during MG reprogramming, and positively to cause cycle exit of MGPCs. Our study reveals unique mechanistic involvement of Oct4, during MG reprogramming and cell cycle exit in zebrafish, which may also account for the inefficient retina regeneration in mammals.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mi4TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    1 - 9 of 9
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    Fish
    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab2-hdac1polyclonal
      IgGRabbit
      Ab4-pou5f3polyclonal
        Rabbit
        Ab16-sox2polyclonal
          IgGRabbit
          1 - 3 of 3
          Show
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          GFPEFGGFP
          1 - 1 of 1
          Show
          Mapping
          No data available