Lensch M William, Daheron Laurence, Schlaeger Thorsten M
Division of Hematology/Oncology, Children's Hospital Boston, Boston, MA 02115, USA.
Stem Cell Rev. 2006;2(3):185-201. doi: 10.1007/s12015-006-0047-2.
The ability of stem cells to self-renew and to replace mature cells is fundamental to ontogeny and tissue regeneration. Stem cells of the adult organism can be categorized as mono-, bi-, or multipotent, based on the number of mature cell types to which they can give rise. In contrast, pluripotent stem cells of the early embryo have the ability to form every cell type of the adult body. Permanent lines of pluripotent stem cells have been derived from preimplantation embryos (embryonic stem cells), fetal primordial germ cells (embryonic germ cells), and malignant teratocarcinomas (embryonal carcinoma cells). Cultured pluripotent stem cells can easily be manipulated genetically, and they can be matured into adult-type stem cells and terminally differentiated cell types in vitro, thereby, providing powerful model systems for the study of mammalian embryogenesis and disease processes. In addition, human embryonic stem cell lines hold great promise for the development of novel regenerative therapies. To fully utilize the potential of these cells, we must first understand the mechanisms that control pluripotent stem cell fate and function. In recent decades, the microenvironment or niche has emerged as particularly critical for stem cell regulation. In this article, we review how pluripotent stem cell signal transduction mechanisms and transcription factor circuitries integrate information provided by the microenvironment. In addition, we consider the potential existence and location of adult pluripotent stem cell niches, based on the notion that a revealing feature indicating the presence of stem cells in a given tissue is the occurrence of tumors whose characteristics reflect the normal developmental potential of the cognate stem cells.
干细胞自我更新和替代成熟细胞的能力对于个体发育和组织再生至关重要。成体生物的干细胞可根据其能够产生的成熟细胞类型数量分为单能、双能或多能干细胞。相比之下，早期胚胎的多能干细胞能够形成成体身体的每一种细胞类型。多能干细胞的永久系已从植入前胚胎（胚胎干细胞）、胎儿原始生殖细胞（胚胎生殖细胞）和恶性畸胎瘤（胚胎癌细胞）中获得。培养的多能干细胞可以很容易地进行基因操作，并且它们可以在体外成熟为成体类型的干细胞和终末分化细胞类型，从而为研究哺乳动物胚胎发生和疾病过程提供强大的模型系统。此外，人类胚胎干细胞系在新型再生疗法的开发方面具有巨大潜力。为了充分利用这些细胞的潜力，我们必须首先了解控制多能干细胞命运和功能的机制。近几十年来，微环境或生态位已成为干细胞调控的特别关键因素。在本文中，我们综述了多能干细胞信号转导机制和转录因子网络如何整合微环境提供的信息。此外，基于在给定组织中表明干细胞存在的一个显著特征是出现其特征反映同源干细胞正常发育潜力的肿瘤这一观点，我们考虑了成体多能干细胞生态位的潜在存在和位置。
