This study investigates the reprogramming of adult pancreatic exocrine cells into β-cells in vivo using a combination of three transcription factors: Ngn3, Pdx1, and MafA. The researchers identified that these factors can induce the formation of insulin-producing cells that closely resemble endogenous islet β-cells in terms of size, shape, and ultrastructure. These induced β-cells express essential β-cell genes and can ameliorate hyperglycemia by remodeling local vasculature and secreting insulin. The study provides evidence that a specific combination of transcription factors can directly convert adult exocrine cells into functional β-cells without the need for dedifferentiation or reversion to a pluripotent state. This approach suggests a general paradigm for directing adult cell reprogramming in vivo, which could have significant implications for regenerative medicine.This study investigates the reprogramming of adult pancreatic exocrine cells into β-cells in vivo using a combination of three transcription factors: Ngn3, Pdx1, and MafA. The researchers identified that these factors can induce the formation of insulin-producing cells that closely resemble endogenous islet β-cells in terms of size, shape, and ultrastructure. These induced β-cells express essential β-cell genes and can ameliorate hyperglycemia by remodeling local vasculature and secreting insulin. The study provides evidence that a specific combination of transcription factors can directly convert adult exocrine cells into functional β-cells without the need for dedifferentiation or reversion to a pluripotent state. This approach suggests a general paradigm for directing adult cell reprogramming in vivo, which could have significant implications for regenerative medicine.