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胚胎发生和畸胎瘤形成中的多能细胞。

Pluripotent cells in embryogenesis and in teratoma formation.

作者信息

Gordeeva O F

机构信息

Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119991, Russia.

出版信息

J Stem Cells. 2011;6(1):51-63.

Abstract

Pluripotent cells of the early preimplantation embryo originate all types of somatic cell and germ cells of the adult organism. Permanent pluripotent cell lines (ES and EG cells) that were derived from an inner cell mass of blastocysts and primordial germ cells have a high proliferative potential and ability to differentiate in vitro into a wide variety of somatic and extraembryonic tissues as well as germ cells and to contribute to different organs of chimeric animals. In some cases pluripotent cells and primordial germ cells can generate teratomas, teratocarsinomas and some kinds of seminomas as the results of damages of differentiation programme of these cells. Experimental teratomas which formed after transplantation of undifferentiated ES and EG cells into immunocompromiced mice may provide a unique opportunity to study pluripotent cell specification and to develop novel approaches in carcinogenesis investigations. Research of signaling and metabolic pathways regulating the pluripotent cell maintenance and their multilineage differentiation are essential to search molecular targets to eliminate undifferentiated cells in tumors. Analysis of interactions between pluripotent cells and differentiated cells of the recipient animals, identification of the factors that may drive differentiation ES and EG cells in vivo contribute in understanding the mechanisms involved in the determination of cell fate during normal development and tumorigenesis. These data are important for development of effective and safe stem cell based technologies for prospective clinical treatment.

摘要

植入前早期胚胎的多能细胞可分化为成年生物体的所有类型体细胞和生殖细胞。从囊胚内细胞团和原始生殖细胞衍生而来的永久性多能细胞系(ES细胞和EG细胞)具有很高的增殖潜力,能够在体外分化为多种体细胞、胚外组织以及生殖细胞,并参与嵌合动物不同器官的形成。在某些情况下,多能细胞和原始生殖细胞由于其分化程序受损,可形成畸胎瘤、畸胎癌和某些类型的精原细胞瘤。将未分化的ES细胞和EG细胞移植到免疫缺陷小鼠体内后形成的实验性畸胎瘤,可能为研究多能细胞特化以及开发癌症发生研究的新方法提供独特的机会。研究调节多能细胞维持及其多谱系分化的信号传导和代谢途径,对于寻找消除肿瘤中未分化细胞的分子靶点至关重要。分析多能细胞与受体动物分化细胞之间的相互作用,鉴定可能驱动ES细胞和EG细胞在体内分化的因子,有助于理解正常发育和肿瘤发生过程中细胞命运决定所涉及的机制。这些数据对于开发有效且安全的基于干细胞的前瞻性临床治疗技术具有重要意义。

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