PUBLICATION

Tel2 regulates redifferentiation of bipotential progenitor cells via Hhex during zebrafish liver regeneration

Authors
Zhang, J., Zhou, Y., Li, S., Mo, D., Ma, J., Ni, R., Yang, Q., He, J., Luo, L.
ID
ZDB-PUB-220407-4
Date
2022
Source
Cell Reports   39: 110596 (Journal)
Registered Authors
He, Jianbo, Luo, Lingfei
Keywords
CP: Cell biology, biliary epithelial cell, hhex, liver, tel2, transdifferentiation
MeSH Terms
  • Zebrafish Proteins/genetics
  • Animals
  • Liver
  • Repressor Proteins
  • Zebrafish/physiology
  • Liver Regeneration*/physiology
  • Stem Cells
  • Hepatocytes
  • Biliary Tract*
(all 9)
PubMed
35385752 Full text @ Cell Rep.
Abstract
Upon extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via biliary epithelial cell (BEC) transdifferentiation, which includes dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and then redifferentiation of BP-PCs to nascent hepatocytes and BECs. This BEC-driven liver regeneration involves reactivation of hepatoblast markers, but the underpinning mechanisms and their effects on liver regeneration remain largely unknown. Using a zebrafish extensive hepatocyte ablation model, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a liver regeneration mutant, liver logan (lvl), in which the telomere maintenance 2 (tel2) gene is mutated. During liver regeneration, the tel2 mutation specifically inhibits transcriptional activation of a hepatoblast marker, hematopoietically expressed homeobox (hhex), in BEC-derived cells, which blocks BP-PC redifferentiation. Mechanistic studies show that Tel2 associates with the hhex promoter region and promotes hhex transcription. Our results reveal roles of Tel2 in the BP-PC redifferentiation process of liver regeneration by activating hhex.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
cq109nTg/cq109nTg; cq127Tg/cq127Tg; cq1Tg/cq1Tgheat shock, chemical treatment by environment: metronidazoleDay 5 to Days 7-13
cq109nTg/cq109nTg; cq127Tg/cq127Tg; cq1Tg/cq1Tgheat shock, chemical treatment by environment: metronidazoleDay 5 to Days 7-13
cq109nTg/cq109nTg; cq127Tg/cq127Tg; cq1Tg/cq1Tgheat shock, chemical treatment by environment: metronidazoleDay 5 to Days 7-13
cq1Tg/cq1Tgchemical treatment by environment: metronidazolePrim-5 to High-pec
cq1Tg/cq1Tgchemical treatment by environment: metronidazolePrim-5 to High-pec
hhexcq124/+; cq1Tg/cq1Tgstandard conditionsDay 5 to Days 7-13
hhexcq124/+; cq1Tg/cq1Tgchemical treatment by environment: metronidazoleDay 5 to Days 7-13
hhexcq124/+; cq1Tg/cq1Tgchemical treatment by environment: metronidazoleDay 5 to Days 7-13
hhexcq124/+; cq1Tg/cq1Tgchemical treatment by environment: metronidazoleDay 5 to Days 7-13
hhexcq124/cq124; cq1Tg/cq1Tgstandard conditionsDay 5 to Days 7-13
1 - 10 of 59
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cq1TgTransgenic Insertion
    cq2TgTransgenic Insertion
      cq109nTgTransgenic Insertion
        cq115TgTransgenic Insertion
          cq122
            Point Mutation
            cq123
              Small Deletion
              cq124
                Indel
                cq125TgTransgenic Insertion
                  cq126TgTransgenic Insertion
                    cq127TgTransgenic Insertion
                      1 - 10 of 13
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      hhexCRISPR2-hhexCRISPR
                      telo2CRISPR1-telo2CRISPR
                      1 - 2 of 2
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CeruleanEFGCerulean
                      CreEFGCre
                      Dendra2EFGDendra2
                      GFPEFGGFP
                      mCherryEFGmCherry
                      NTREFGNTR
                      TomatoEFGTomato
                      VenusEFGVenus
                      1 - 8 of 8
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                      Mapping
                      No data available