Notch signaling dependent differentiation of cholangiocyte-like cells from rhesus monkey embryonic stem cells

	Notch signaling dependent differentiation of cholangiocyte-like cells from rhesus monkey embryonic stem cells
	Jin LF 1,2; Ji SH 2; Yang JF 2,3; Ji WZ[*]2
刊名	动物学研究
	2011
卷号	32 期号:4 页码:391-395
关键词	Rhesus monkey Embryonic stem cells Cholangiocytes Notch signaling
其他题名	Notch 信号通路调控猕猴胚胎干细胞的胆管样细胞分化
通讯作者	wji@mail.kiz.ac.cn
中文摘要	猕猴胚胎干细胞(rhesus monkey embryonic stem(rES))与人胚胎干细胞有相似的生物学特性,因此是理想的临床前研究的替代模型。Notch信号通路在胆管及胆管上皮细胞的形成中有重要的作用,然而,有关Notch信号通路在ES细胞的胆向分化中的作用了解甚少。该实验以rES为模型,对Notch信号通路对ES细胞的胆向分化过程中的作用进行了较为系统的研究。rES在细胞因子ActivinA诱导作用下产生约80%的限定性内胚层细胞。以Matrigel作为细胞外基质,在含BMP4和FGF1的无血清培养体系中继续诱导5～7d,rES细胞来源的限定性内胚层细胞分化产生约胆管样细胞。分化的细胞表达胆管细胞的特异性蛋白((CK7、CK18、CK19、CK20和OV-6)及基因(GSTPi、IB4和HNF1β)。在胆管样细胞的分化过程中检测到了Notch1和Notch2基因及下游信号分子hes1和hes5的表达。用Notch抑制剂L-685458处理分化过程中的细胞可导致Notch1和Notch2基因及下游信号分子hes1和hes5的表达下降,同时CK19阳性的胆管样细胞分化比率也从90%下降至约20%。这一研究提示Notch信号通路可能在ES细胞的胆管样分化过程中扮演重要的角色。
英文摘要	Rhesus monkey embryonic stem (rES) cells have similar characteristics to human ES cells, and might be useful as a substitute model for preclinical research. Notch signaling is involved in the formation of bile ducts, which are composed of cholangiocytes. However, little is known about the role of Notch signaling in cholangiocytic commitment of ES cells. We analyzed the effect of Notch signaling on the induction of cholangiocyte-like cells from rES cells. About 80% of definitive endoderm (DE) cells were generated from rES cells after treatment with activin A. After treatment with BMP4 and FGF1 on matrigel coated wells in serum-free medium, rES-derived DE gave rise to cholangiocyte-like cells by expression of cholangiocytic specific proteins (CK7, CK18, CK19, CK20, and OV-6) and genes (GSTPi, IB4, and HNF1β). At the same time, expression of Notch 1 and Notch 2 mRNA were detected during cell differentiation, as well as their downstream target genes such as Hes 1 and Hes 5. Inhibition of the Notch signal pathway by L-685458 resulted in decreased expression of Notch and their downstream genes. In addition, the proportion of cholangiocyte-like cells declined from ~90% to ~20%. These results suggest that Notch signaling may play a critical role in cholangiocytic development from ES cells.
收录类别	CSCD
资助信息	This work was supported by research grants from Zhejiang Natural Sciences Foundation of China (Y2110911; Y2080996), and the National Key Technologies R&D Program of China (2007CB947701)
语种	英语
公开日期	2012-09-14
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/7100]
专题	昆明动物研究所_生殖与发育生物学
作者单位	1.College of Life Science of Shaoxing University, Shaoxing Zhejiang 312000, China 2.Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming Yunnan 650223, China 3.College of Life Science of Wenzhou Medical College, Shaoxing Zhejiang 325035, China
推荐引用方式 GB/T 7714	Jin LF,Ji SH,Yang JF,et al. Notch signaling dependent differentiation of cholangiocyte-like cells from rhesus monkey embryonic stem cells[J]. 动物学研究,2011,32(4):391-395.
APA	Jin LF,Ji SH,Yang JF,&Ji WZ[*].(2011).Notch signaling dependent differentiation of cholangiocyte-like cells from rhesus monkey embryonic stem cells.动物学研究,32(4),391-395.
MLA	Jin LF,et al."Notch signaling dependent differentiation of cholangiocyte-like cells from rhesus monkey embryonic stem cells".动物学研究 32.4(2011):391-395.