Reprogramming Pancreatic Cells

In vivo reprogramming of adult pancreatic exocrine cells to β -cells Qiao Zhou, Juliana Brown, Andrew Kanarek, Jayaraj Rajagopal & Douglas A. Melton . Nature (2008),455: 627-633 Presenter: Richard Myers, HHMI-IMBS

A Brief History of Key Reprogramming Experiments ,[object Object],[object Object],[object Object],[object Object],[object Object]

Cells of the Pancreas Insulin-secreting β -cells are found in the islets of Langerhans which are surrounded by exocrine cells

Cells of the Pancreas ,[object Object],[object Object],[object Object]

Exocrine cells and β -cells Exocrine acinar cells secrete amylase into the pancreatic duct leading to the gut β -cells in islet of Langerhans secrete insulin into the blood

Reprogramming adult pancreatic cells ,[object Object],[object Object],[object Object],[object Object],Pdx1 Mafa Ngn3 Exocrine Acinar Cell Induced β -Cell M3 adenovirus TF cocktail

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A combination of three transcription factors induces insulin + cells in adult mouse pancreas in vivo . ,[object Object],[object Object],[object Object],[object Object]

Induced new β -cells originate from differentiated exocrine cells ,[object Object],[object Object],[object Object],[object Object]

Endogenous and induced β -cells are indistinguishable in morphology and ultrastructure. ,[object Object],[object Object],[object Object],[object Object],Insulin granules visible as opposed to zymogen (amylase) granules

Molecular marker characterization of induced β -cells. ,[object Object],[object Object],[object Object],Expression patterns of induced β -cells

Type 1 diabetes mellitus ,[object Object],[object Object],[object Object]

Induced new β -cells remodel vasculature and ameliorate hyperglycemia. ,[object Object],[object Object],M3 reduces blood glucose levels in hyperglycemic STZ diabetic mouse models Triangle: non-diabetic control Square: diabetic STZ mice Diamond: M3 treated diabetic STZ mice Increases in insulin and β -cells is small compared to WT but significant compared to diabetic mice

Supplementary Information ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Some Problems to Address ,[object Object],[object Object],[object Object],[object Object]

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Reprogramming Pancreatic Cells

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