2012年的诺贝尔生理/医学奖颁给了英国科学家约翰•戈登（John B. Gurdon）和日本科学家山中伸弥（Shinya Yamanaka）获奖，获奖理由是“成熟细胞可被重编程恢复多能性”。这种技术的关键就在于利用四种转录因子令体细胞重新获得多能性。
科学家揭示细菌诱导胃细胞转分化肠细胞的分子机制
经过多年的研究，其诱导转录因子已经被发现可以用多种成分来代替，有的研究人员将其减少为了三种，两种，有的研究人员则利用蛋白来实现诱导作用，然而近期来自东京大学的一组研究人员却发现了幽门螺杆菌具有令体细胞恢复未分化细胞，回到干细胞状态的类似作用，引起了多方的关注。相关成果公布在《美国国家科学院院刊》（PNAS）杂志上。
幽门螺杆菌（Helicobacter pylori）是从胃黏膜中分离出来的一种弯曲样杆菌。现已确认与慢性胃炎、消化性溃疡病、低度恶性的胃钻膜相关淋巴组织淋巴瘤和胃癌密切相关。
研究显示幽门螺杆菌的慢性感染是胃黏膜肠化的主要原因，而且会受到肠特异性骶管相关同源异形盒 (CDX) 转录因子的异常诱导，其中CDX1和CDX2在这种肠化作用中扮演了重要角色。那么这些作用因子如何直接调控这种细胞，组织特异性开关的呢？
在这篇文章中，研究人员分析胃上皮细胞中被CDX1直接激活的基因，并从中找到了与重编程因子：SALL4 和 KLF5有关的干性特征，也就是说，当幽门螺杆菌表达的蛋白进入胃上皮细胞之后，CDX1就会激活这两种基因，从而胃上皮细胞就会重编程成为一种类似干细胞，能发育成消化道各种细胞的干性细胞。
通过进一步分析，研究人员还发现抑制SALL4 或KLF5的表达，就会导致这种特性消失，这从侧面也证明了CDX1诱导的SALL4和KLF5能逆转胃上皮细胞转变成类似干细胞的祖细胞。
这也解释了为什么长期出现幽门螺杆菌感染造成的慢性胃炎，胃粘膜上就会出现肠道细胞，研究人员认为这可能是由于重编程为类似干细胞状态的细胞分裂出了肠道细胞。
这些研究均表明，幽门螺杆菌具有令体细胞恢复未分化细胞，回到干细胞状态的类似作用，而且由于干细胞也具有癌变的性质，因此这项研究也指出了此种感染与癌变的可能。
CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5
Yumiko Fujiia,Kyoko Yoshihashia,Hidekazu Suzukic,Shuichi Tsutsumid,Hiroyuki Mutohe,Shin Maedaf,Yukinori Yamagatag,Yasuyuki Setog,Hiroyuki Aburatanid, andMasanori Hatakeyamaa
Intestinal metaplasia of the stomach, a mucosal change characterized by the conversion of gastric epithelium into an intestinal phenotype, is a precancerous lesion from which intestinal-type gastric adenocarcinoma arises. Chronic infection with Helicobacter pylori is a major cause of gastric intestinal metaplasia, and aberrant induction by H. pylori of the intestine-specific caudal-related homeobox (CDX) transcription factors, CDX1 and CDX2, plays a key role in this metaplastic change. As such, a critical issue arises as to how these factors govern the cell- and tissue-type switching. In this study, we explored genes directly activated by CDX1 in gastric epithelial cells and identified stemness-associated reprogramming factors SALL4 and KLF5. Indeed, SALL4 and KLF5 were aberrantly expressed in the CDX1+ intestinal metaplasia of the stomach in both humans and mice. In cultured gastric epithelial cells, sustained expression of CDX1 gave rise to the induction of early intestinal-stemness markers, followed by the expression of intestinal-differentiation markers. Furthermore, the induction of these markers was suppressed by inhibiting either SALL4 or KLF5 expression, indicating that CDX1-induced SALL4 and KLF5 converted gastric epithelial cells into tissue stem-like progenitor cells, which then transdifferentiated into intestinal epithelial cells. Our study places the stemness-related reprogramming factors as critical components of CDX1-directed transcriptional circuitries that promote intestinal metaplasia. Requirement of a transit through dedifferentiated stem/progenitor-like cells, which share properties in common with cancer stem cells, may underlie predisposition of intestinal metaplasia to neoplastic transformation.
