Jagged-1抑制小鼠胚胎干细胞分化为造血干/祖细胞  

Jagged-1 inhibits mouse embryonic stem cells differentiating into haematopoietic stem or progenitor cells

作　　者：陈日玲 郑伟荣 谭霖 刘东强 史惠 陈启康 CHEN Ri-lin;ZHENG Wei-rong;TAN Lin;LIU Dong-qiang;SHI Hui;CHEN Qi-kang(Department of Pediatrics,the Affiliated Shunde Women and Children Hospital, Guangdong Medical University, Shunde 528300;Department of Pediatrics, the First Hospital of Quanzhou,Quanzhou 362000;Children's Medical Center,the Affiliated Hospital of Guangdong Medical University, Zhanjiang 524023, China)

机构地区：[1]广东医科大学附属顺德妇女儿童医院儿科,广东顺德528300 [2]泉州市第一医院儿科,福建泉州362000 [3]广东医科大学附属医院儿童医学中心,广东湛江524023

出　　处：《基础医学与临床》2021年第1期55-61,共7页Basic and Clinical Medicine

基　　金：湛江市科技竞争性项目(2014A01022)。

摘　　要：目的探讨Notch信号通路在小鼠胚胎干细胞(ESC)分化为造血干/祖细胞(HSC/HPC)中的作用。方法1)体外培养小鼠拟胚体细胞(EBs),使用Jagged-1蛋白活化Notch信号通路及DAPT(γ-分泌酶抑制剂)抑制Notch信号通路。实验分为拟胚体细胞复苏组(EB组)、对照组、Jagged-1组、DAPT组和Jagged-1-DAPT组。2)流式细胞计量术检测ESC特异性表型和HSC/HPC特异性表型的表达。3)实时定量PCR检测各组Notch信号通路基因、小鼠ESC表型基因和HSC/HPC表型基因的表达。结果1)Jagged-1组细胞胚胎干细胞数较对照组和Jagged-1-DAPT组明显增多(P<0.05),2)Jagged-1-DAPT组分化的HSC/HPC数较control组及Jagged-1组明显增多(P<0.05);3)Jagged-1组Notch1、Notch2、Notch4 mRNA表达量较对照组明显升高(P<0.05);4)DAPT组和Jagged-1-DAPT组中Notch1、Notch4 mRNA表达量较对照组降低(P<0.05)。结论Jagged-1激活Notch信号通路可抑制小鼠ESC向HSC/HPC的分化。Objective To investigate the effect of Notch signaling pathways on differentiation of mouse embryonic stem cells(ESC)into haematopoietic stem or progenitor cells(HSC/HPC).Methods 1)incubate mouse embryoid body cells and divide the embryonic stem cells into five groups as EB group,control group,Jagged-1 group,DAPT group and Jagged-1-DAPT group.2)detect the phenotype of HSC/HPC by flow cytometry.3)The expression of Notch signaling pathway,mouse embryonic stem cell phenotype and HSC/HPC phenotype were detected by RT-PCR.Results 1)the number of embryonic stem cells in Jagged-1 group was significantly more than that in control group and Jagged-DAPT group(P<0.05);2)the number of HSC/HPC in Jagged-1-DAPT group was significantly more than that in control group and in Jagged-1 group(P<0.05);3)the expression of Notch1,Notch2and Notch4 mRNA in Jagged-1 group was significantly higher than that in control group(P<0.05),4)the expression of Notch1 and Notch4 mRNA in DAPT group and Jagged-1-DAPT group was lower than that in control group(P<0.05).Conclusions Jagged-1 activation of Notch signaling pathway potentially inhibits ESC differentiation into HSC/HPC in mice model.

关 键 词：胚胎干细胞 NOTCH信号通路 造血干细胞 JAGGED-1 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] Q253[医药卫生—基础医学]