Olfm4^(+)小肠干细胞清除小鼠模型的构建及其效果评估  

Remove Olfm4^(+) Intestinal Stem Cells in Mice Modelwas Constructed and Evaluate Its Effects on Mice Survival Development after Birth

作　　者：施晨怡 赵冰 SHI Chenyi;ZHAO Bing(State Key Laboratory of Genetic Engineering,School of Life Sciences,Fudan University,Shanghai 200433,China)

机构地区：[1]复旦大学生命科学学院遗传工程国家重点实验室,上海200433

出　　处：《复旦学报（自然科学版）》2024年第2期268-275,共8页Journal of Fudan University：Natural Science

基　　金：国家重点研发计划“干细胞及转化研究”重点专项(2018YFA0109400)。

摘　　要：小肠是人体中负责消化吸收的主要器官,其具有强大的自我更新能力,主要得益于小肠隐窝基底部的小肠干细胞,平均3~7天就会完全更新一次。LGR5是小肠干细胞最典型的标志物,而嗅素4(Olfactomedin 4,Olfm4)是新的小肠干细胞标志物,在出生后阶段其与LGR5的表达会有差异。成体中,当LGR5^(+)小肠干细胞受到损伤时,^(+)4储备干细胞、肠分泌细胞等可以转变为LGR5^(+)小肠干细胞来补充LGR5^(+)小肠干细胞的损失。为了探究在出生后发育阶段LGR5^(+)小肠干细胞并未成熟时,是否会有某种细胞类群补充小肠干细胞对功能,借助转基因小鼠,在出生后9天开始杀死Olfm4^(+)小肠干细胞,并通过HE染色、QPCR和免疫组化等方法鉴定小肠功能。结果显示,在出生后阶段杀伤Olfm4^(+)小肠干细胞,并不会影响小肠结构和小鼠的存活,并猜测可能是Sox9阳性的小肠祖细胞补偿了Olfm4^(+)小肠干细胞的功能。The small intestine is the main organ responsible for digestion and absorption in the human body.It has a strong self-renewal ability,relying on LGR5^(+)small intestine stem cells at the bottom of the glandular fossa.It will completely renew once in 3—7 days on average.LGR5 is the most typical marker of intestinal stem cells and olfactomedin 4(Olfm4)is a new markers of small intestinal stem cell,having different expression with the LGR5 after birth stage.In adults,when LGR5^(+)small intestinal stem cells are damaged,^(+)4 reserve stem cells and intestinal secretory cells can be converted into LGR5^(+)small intestinal stem cells to supplement the loss of LGR5^(+)small intestinal stem cells.In order to investigate whether there is a cell group that can supplement the function of LGR5^(+)small intestinal stem cells in postnatal development when LGR5^(+)small intestinal stem cells are not mature,transgenic mice were used to kill Olfm4^(+)small intestinal stem cells at 9 days after birth,and the intestinal function was determined by HE staining,qPCR and immunohistochemistry.The results showed that killing Olfm4^(+)small intestinal stem cells at postnatal stage did not affect Small intestinal structure and mouse survival,and it was speculated that Sox9 positive small intestinal progenitor cells might compensate for the function of Olfm4^(+)small intestinal stem cells.

关 键 词：小肠干细胞 出生后发育 Olfm4 SOX9 

分 类 号：Q34[生物学—遗传学]