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Context-specific α- to-β-cell reprogramming by forced Pdx1 expression

Yang, Yu-Ping
Boyer, Daniel F
Wright, Christopher V E
Published in Genes and Development. 2011, vol. 25, no. 16, p. 1680-5
Abstract Using single transcription factors to reprogram cells could produce important insights into the epigenetic mechanisms that direct normal differentiation, or counter inappropriate plasticity, or even provide new ways of manipulating normal ontogeny in vitro to control lineage diversification and differentiation. We enforced Pdx1 expression from the Neurogenin-3-expressing endocrine commitment point onward and found during the embryonic period a minor increased β-cell allocation with accompanying reduced α-cell numbers. More surprisingly, almost all remaining Pdx1-containing glucagon/Arx-producing cells underwent a fairly rapid conversion at postnatal stages, through glucagon-insulin double positivity, to a state indistinguishable from normal β cells, resulting in complete α-cell absence. This α-to-β conversion was not caused by activating Pdx1 in the later glucagon-expressing state. Our findings reveal that Pdx1 can work single-handedly as a potent context-dependent autonomous reprogramming agent, and suggest a postnatal differentiation evaluation stage involved in normal endocrine maturation.
Keywords AnimalsAnimals, NewbornBasic Helix-Loop-Helix Transcription Factors/genetics/metabolismFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGlucagon/genetics/metabolismGlucagon-Secreting Cells/cytology/metabolismHomeodomain Proteins/genetics/metabolismImmunohistochemistryInsulin/genetics/metabolismInsulin-Secreting Cells/cytology/metabolismLuminescent Proteins/genetics/metabolismMaleMiceMice, KnockoutMice, TransgenicNerve Tissue Proteins/genetics/metabolismPancreas/embryology/growth & development/metabolismReverse Transcriptase Polymerase Chain ReactionTrans-Activators/genetics/metabolism
PMID: 21852533
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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YANG, Yu-Ping et al. Context-specific α- to-β-cell reprogramming by forced Pdx1 expression. In: Genes & development, 2011, vol. 25, n° 16, p. 1680-5. doi: 10.1101/gad.16875711 https://archive-ouverte.unige.ch/unige:25633

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Deposited on : 2013-01-17

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