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Propensity of Human Embryonic Stem Cell Lines During Early Stage of Lineage Specification Controls Their Terminal Differentiation into Mature Cell Types

胚胎干细胞 胚状体 生物 细胞生物学 细胞分化 P19电池 中胚层 细胞培养 干细胞 电池类型 遗传学 细胞 成体干细胞 基因
作者
Rajarshi Pal,Swapnil Totey,Murali Krishna Mamidi,Vijay Bhat,S.M. Totey
出处
期刊:Experimental Biology and Medicine [SAGE Publishing]
卷期号:234 (10): 1230-1243 被引量:36
标识
DOI:10.3181/0901-rm-38
摘要

Human embryonic stem cells (hESCs) are able to stably maintain their characteristics for an unlimited period; nevertheless, substantial differences among cell lines in gene and protein expression not manifested during the undifferentiated state may appear when cells differentiate. It is widely accepted that developing an efficient protocol to control the differentiation of hESCs will enable us to produce adequate numbers of desired cell types with relative ease for diverse applications ranging from basic research to cell therapy and drug screening. Hence of late, there has been considerable interest in understanding whether and how hESC lines are equivalent or different to each other in their in vitro developmental tendencies. In this study, we compared the developmental competences of two hESC lines (HUES-9 and HUES-7) at molecular, cellular and functional levels, upon spontaneous differentiation without any added inducing agents. Both cell lines generated the three embryonic germ layers, extra-embryonic tissues and primordial germ cells during embryoid body (EB) formation. However HUES-9 showed a stronger propensity towards formation of neuroectodermal lineages, whereas HUES-7 differentiated preferentially into mesoderm and endoderm. Upon further differentiation, HUES-9 generated largely neural cells (neurons, oligodendrocytes, astrocytes and gangliosides) whereas HUES-7 formed mesendodermal derivatives, including cardiomyocytes, skeletal myocytes, endothelial cells, hepatocytes and pancreatic cells. Overall, our findings endorse the hypothesis that independently-derived hESCs biologically differ among themselves, thereby displaying varying differentiation propensity. These subtle differences not only highlight the importance of screening and deriving lines for lineage-specific differentiation but also indicate that individual lines may possess a repertoire of capabilities that is unique.

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