Sakaki-Yumoto Masayo, Katsuno Yoko, Derynck Rik
Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, CA 94143-0669, USA.
Biochim Biophys Acta. 2013 Feb;1830(2):2280-96. doi: 10.1016/j.bbagen.2012.08.008. Epub 2012 Aug 16.
The diversity of cell types and tissue types that originate throughout development derives from the differentiation potential of embryonic stem cells and somatic stem cells. While the former are pluripotent, and thus can give rise to a full differentiation spectrum, the latter have limited differentiation potential but drive tissue remodeling. Additionally cancer tissues also have a small population of self-renewing cells with stem cell properties. These cancer stem cells may arise through dedifferentiation from non-stem cells in cancer tissues, illustrating their plasticity, and may greatly contribute to the resistance of cancers to chemotherapies.
The capacity of the different types of stem cells for self-renewal, the establishment and maintenance of their differentiation potential, and the selection of differentiation programs are greatly defined by the interplay of signaling molecules provided by both the stem cells themselves, and their microenvironment, the niche. Here we discuss common and divergent roles of TGF-β family signaling in the regulation of embryonic, reprogrammed pluripotent, somatic, and cancer stem cells.
Increasing evidence highlights the similarities between responses of normal and cancer stem cells to signaling molecules, provided or activated by their microenvironment. While TGF-β family signaling regulates stemness of normal and cancer stem cells, its effects are diverse and depend on the cell types and physiological state of the cells.
Further mechanistic studies will provide a better understanding of the roles of TGF-β family signaling in the regulation of stem cells. These basic studies may lead to the development of a new therapeutic or prognostic strategies for the treatment of cancers. This article is part of a Special Issue entitled Biochemistry of Stem Cells.
在整个发育过程中产生的细胞类型和组织类型的多样性源自胚胎干细胞和体细胞干细胞的分化潜能。前者具有多能性,因此能够产生完整的分化谱系,而后者的分化潜能有限,但驱动组织重塑。此外,癌组织中也有一小部分具有干细胞特性的自我更新细胞。这些癌症干细胞可能通过癌组织中非干细胞的去分化产生,这说明了它们的可塑性,并且可能极大地促成癌症对化疗的抗性。
不同类型干细胞的自我更新能力、其分化潜能的建立和维持以及分化程序的选择,在很大程度上由干细胞自身及其微环境(生态位)提供的信号分子之间的相互作用所决定。在这里,我们讨论转化生长因子-β(TGF-β)家族信号在调节胚胎干细胞、重编程多能干细胞、体细胞干细胞和癌症干细胞中的共同和不同作用。
越来越多的证据凸显了正常干细胞和癌症干细胞对其微环境提供或激活的信号分子反应之间的相似性。虽然TGF-β家族信号调节正常干细胞和癌症干细胞的干性,但其作用是多样的,并且取决于细胞类型和细胞的生理状态。
进一步的机制研究将有助于更好地理解TGF-β家族信号在调节干细胞中的作用。这些基础研究可能会促成开发用于治疗癌症的新治疗或预后策略。本文是名为“干细胞生物化学”的特刊的一部分。