Molecular Control of Pancreatic Beta Cell Reprogramming

近年来，细胞重编程已成为再生医学中一种有前途的方法， 身体中丰富的成体细胞被转化为医学上重要的细胞类型，以修复由于 疾病或伤害。这种方法对于开发1型糖尿病的治疗方法很有价值， 这是由于自身免疫破坏了分泌胰岛素的β细胞。本提案的长期目标是 了解控制β细胞重编程的细胞和分子机制。我们将采取 最近开发的模型系统的优点，其中少量的转录因子重编程成人 外分泌细胞转化为β细胞在具体目标I中，我们将确定每一个功能的贡献， 重编程因子对β细胞重编程过程的影响。在目的II中，我们将确定重编程因子和染色质重塑基因之间的功能和物理相互作用。在目标III中，我们将确定外分泌身份基因是否作为β细胞重编程的分子屏障。这些拟议的研究有望揭示控制β细胞重编程的分子机制。 这些分子学的见解将允许更好地控制重编程过程，并有助于开发新的细胞替代疗法来治疗1型糖尿病。

Cellular reprogramming has emerged in recent years as a promising approach in regenerative medicine whereby abundant adult cells ofthe body are converted into medically important cell types to repair tissues lost due to disease or injury. This approach could prove valuable for developing treatments for Type 1 diabetes, a disease that results from autoimmune destruction of insulin secreting beta cells. The long term goal of this proposal is to understand the cellular and molecular mechanisms that control beta cell reprogramming. We will take advantage of a recently developed model system where a small number of transcription factors reprogram adult exocrine cells into beta cells. In Specific Aim I, we will determine the functional contribution of each reprogramming factor to the beta cell reprogramming process. In Aim II, we will determine the functional and physical interactions between reprogramming factors and chromatin remodeling genes. In Aim III, we will determine whether exocrine identity genes act as molecular barriers to beta cell reprogramming. The proposed studies are expected to shed important light on the molecular mechanisms that control beta cell reprogramming. Such molecular insights will allow better control ofthe reprogramming process and aid the development of novel cell replacement therapies to treat Type 1 diabetes.