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Table 1 Conditions that promote β-cell regeneration

From: In vivo generation and regeneration of β cells in zebrafish

 InducerEffectsDevelopmental stageCell sourceRelated mechanismModifer ScreenGene/target identifiedRelated pathwayReference
Manipulation of Insulin signalingTransgenic expression of a dominant-negative IGF1RInsulin resistanceEmbrynonic, Larval and adultProgenitors and β cellsProliferationNoneigf1rInsulin signalling(Maddison et al., 2015)
Knockout of insra/insrbInsulin resistanceEmbryonic and larvalUnknownN.A.Noneinsra/insrbInsulin signalling(Yang et al., 2017)
Transgenic expression of a dominant-negative IRS2Insulin resistanceEmbryonicProgenitorsNeogenesisNoneirs2Insulin signalling(Ye et al., 2016)
NutrientIncreased insulin demandlarvalProgenitorsNeogenesisCandidate drugsfgf1/rapamycinFGF, mTORC1(Maddison & Chen, 2012; Li et al., 2014)
NutrientIncreased insulin demandLarvalProgenitors and β cellsNeogenesisCandidate drugsg secretase inhibitor and rapamycinNotch, mTORC1(Ninov et al., 2013)
β-cell ablationDecreased insulin supplyLarvalProgenitors and β cellsNeogenesisChemical libraryAdenosine Receptor A2aa (agonist)Adenosinergic(Andersson et al., 2012; Schulz et al., 2016)
β-cell ablationDecreased insulin supplyLarvalβ cellsProliferationChemical libraryTBK1/IKKε (inhibitor)PKA, mTORC1(Xu et al., 2018)
β-cell ablationDecreased insulin supplyLarvalProgenitorsNeogenesisMutationSox9bRetinoic acid signaling; Notch signaling(Manfroid et al., 2012; Huang et al., 2016)
β-cell ablationDecreased insulin supplyLarvalProgenitorsNeogenesisMutationDnmt1N.A.(Anderson et al., 2009)
β-cell ablationDecreased insulin supplyLarvalProgenitorsNeogenesisMutationfhl1bN.A.(Xu et al., 2016)
β-cell ablationDecreased insulin supplyLarvalα cellsTrandedifferentiationMorpholino, antibodygcgnon-gluconeogenic effects of glucagon(Ye et al., 2015)
β-cell ablationDecreased insulin supplyLarvalα cellsTrandedifferentiationMutationIgfbp1IGF1 signaling(Lu et al., 2016)
Chemical geneticsChemicalsInhibition or activation of drug targetsLarvalProgenitorsNeogenesisNoneALDH1A1 (inhibitor), IMPDH (inhibitor)RA, Nucleotide synthesis(Rovira et al., 2011; Shen et al., 2013)
ChemicalsInhibition or activation of drug targetsLarvalProgenitors and β cellsProliferation/ NeogenesisNoneNFkb activators, Serotonergic activatorsNFkB, Serotonergic, glucorcorticoid analogs(Wang et al., 2015; Janjuha et al., 2018)
ChemicalsInhibition or activation of drug targetsLarvalβ cellsProliferationNoneRXR agonists, serotonin boosters, GR agonistsRA, Serotonergic, glucocorticoid(Tsuji et al., 2014)
Notch inhibitionPrecocious β-cell differentiationLarvalProgenitorsNeogenesisChemical libraryCDK5 (inhibitor)N.A.(Liu et al., 2018)
OtherMicrobiotaUnknownLarvalProgenitorsProliferationlarvae stageBefAN.A.(Hill et al., 2016)
CDK4Cell division activationLarvalβ cellsProliferationlarvae stageCyclin-Dependent Kinase 4N.A.(Li et al., 2013)
Genetic Lineage TracingSuppression of target geneembryonic developmentAcinarTrandedifferentiationNonePtf1αN.A.(Hesselson et al., 2011; Dong et al., 2008)