我们前期研究发现，造血干细胞在动物体内可以分化为胃上皮细胞；红白血病细胞与胃癌细胞中存在相同信号转导通路的反向调控；造血干细胞在胃粘膜局部微环境的诱导下可能通过抑制血细胞蛋白质表达、诱导上皮细胞蛋白质表达实现造血干细胞向上皮的分化，当胃粘膜慢性损伤时，本应沉默的血细胞蛋白质在胃粘膜出现异常表达，胃上皮开始恶性转化。这些结果为胃癌的造血干细胞来源提供了线索。本课题拟运用C-kit启动子调控下的GFP转基因小鼠分选的造血干细胞，在胃炎和胃癌动物模型中，动态跟踪GFP+细胞在胃粘膜的定植和分化；采用单细胞显微切割、转录组测序、生物信息学分析、细胞及分子生物学技术，研究小鼠胃粘膜损伤情况下，造血干细胞向胃上皮分化的关键分子事件及其在胃癌发生中的作用。本项目将首次阐明上述过程中造血干细胞内发生的信号调控网络的变化及其关键节点，阐明慢性胃炎环境下胃癌发生的新机制；为抗胃癌药物研发提供新靶点。

We have previously found that hemopoietic stem cell (HSC) can differentiate into gastric epithelia and same signal transduction network was reversely regulated in erythroleukemia and gastric cancer cells. Our results also suggested that the gastric local factors induce the HSC differentiate into gastric epithelia through suppressing the expression of blood cell-directed proteins and promote the expression of epithelium-directed proteins. Once the gastric mucosa was damaged, the silenced protein in gastric epithelium was unexpectedly expressed and the malignant transformation of gastric epithelium was occurred. These results provide evidence for understanding the HSC-derived gastric carcinogenesis.In this project, we isolate the GFP-expressing HSC from transgene mouse and inject the GFP+ cells to mice who suffer from gastritis or gastric cancer. By using the single cell microdissection，transcriptome sequencing，bioinformatics analysis，cellular and molecular techniques，changes of the key event during the HSC differentiate to the gastric epithelium and its role in gastric carcinogenesis will be dynamically studied. This project will, for the first time clarify the signal transduction network and the key events in HSC-derived gastric epithelium fromation, clarify a novel mechanism for gastric carcinogenesis, and provide novel targets for anti-gastric cancer drug development.