Context-specific alpha-to-beta-cell reprogramming by forced Pdx1 expression

作者：Yang Yu Ping; Thorel Fabrizio; Boyer Daniel F; Herrera Pedro L; Wright Christopher V E^*

来源：Genes & Development, 2011, 25(16): 1680-1685.

DOI：10.1101/gad.16875711

• pancreas
• endocrine progenitors
• alpha and beta cells
• reprogramming
• Pdx1

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 beta-cell allocation with accompanying reduced alpha-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 beta cells, resulting in complete alpha-cell absence. This alpha-to-beta 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.

• 出版日期2011-8-15