Barrett食管（BE）是指食管远端的鳞状上皮被化生的柱状上皮所取代的一种病理现象，与食管腺癌的发生有关，但其发生的分子机制仍不清楚。最近发现，分化成熟的鼠或人的体细胞可以通过过量表达一些转录因子使细胞重新编程为所谓的"诱导性多能干细胞"（induced pluripotent stem cells，iPSC)，端粒在维持胚胎干细胞多潜能性方面可能起起重要作用。据此我们设想，在酸和胆盐的作用下，可以使食管鳞状上皮通过过量表达一些转录因子使细胞重新编程为iPSC，然后再通过"环境依赖的分化作用"进一步分化为BE细胞。在此过程中端粒和端粒酶起重要调控作用。为证实以上设想，我们拟通过体内外实验研究胃酸、胆汁及混合反流物对食管磷状上皮细胞重新编程的影响，并探讨在BE发生过程中端粒-端粒酶途径、转录因子途径的作用，从全新的角度揭示BE细胞学起源及其发生的分子机制，并为BE的防治提供新的探索途径。

Barrett's oesophagus（BE）is a condition where normal squamous epithelium is replaced by metaplastic columnar epithelium，and is a risk factor for the development of oesophageal adenocarcinoma, a cancer with rapidly increasing incidence in developed societies. However，Mechanisms of development of BE remain elusive. Recently，reprogramming of adult differentiated cells to the so-called induced pluripotent stem cells (iPSCs) has been achieved by over expression of specific transcription factors. Rejuvenation of telomeres with various lengths has been found in iPSCs. We hypothesize that normal esophageal squamous epithelium cells can be reprogrammed to iPSCs by induced expression of specific transcription factors，and then differentiate into BE cells through environment-dependent differentiation. To investigate that possibility, we want to study the effects of acid and bile salt on reprogramming of normal squamous epithelium cells into iPSCs and the role of telomere-telomerase and transcription factor pathways in the development of BE in vivo and in vitro. Our study may reveal genesis of BE and explore a new way for prevention and treatment of BE.