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

Yang YP, Thorel F, Boyer DF, Herrera PL, Wright CV
Genes Dev. 2011 25 (16): 1680-5

PMID: 21852533 · PMCID: PMC3165933 · DOI:10.1101/gad.16875711

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.

MeSH Terms (21)

Animals Animals, Newborn Basic Helix-Loop-Helix Transcription Factors Female Gene Expression Profiling Gene Expression Regulation, Developmental Glucagon Glucagon-Secreting Cells Homeodomain Proteins Immunohistochemistry Insulin Insulin-Secreting Cells Luminescent Proteins Male Mice Mice, Knockout Mice, Transgenic Nerve Tissue Proteins Pancreas Reverse Transcriptase Polymerase Chain Reaction Trans-Activators

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