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很有前途的方法 体内丰富的成体细胞转化为具有重要医学意义的细胞类型，以修复因 疾病或伤害。这种方法可能被证明对开发治疗1型糖尿病有价值 这是由于自身免疫破坏了分泌胰岛素的β细胞。这项提议的长期目标是 了解控制β细胞重新编程的细胞和分子机制。我们会带上 最近开发的一个模型系统的优势，其中少量转录因子对成体进行重新编程 将细胞外分泌转化为β细胞。在具体目标I中，我们将确定每个功能的贡献 将重编程因子添加到β单元重编程过程。在AIM 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，我们将确定外分泌识别基因是否作为β细胞重新编程的分子屏障。这项拟议的研究有望为控制β细胞重新编程的分子机制提供重要的线索。 这种分子洞察力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.