Department of Pediatrics, Department of Genetics, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Institute, Stanford, California 94305, USA.
Genes Dev. 2012 Jul 1;26(13):1409-20. doi: 10.1101/gad.193730.112.
Stem cells play a critical role during embryonic development and in the maintenance of homeostasis in adult individuals. A better understanding of stem cell biology, including embryonic and adult stem cells, will allow the scientific community to better comprehend a number of pathologies and possibly design novel approaches to treat patients with a variety of diseases. The retinoblastoma tumor suppressor RB controls the proliferation, differentiation, and survival of cells, and accumulating evidence points to a central role for RB activity in the biology of stem and progenitor cells. In some contexts, loss of RB function in stem or progenitor cells is a key event in the initiation of cancer and determines the subtype of cancer arising from these pluripotent cells by altering their fate. In other cases, RB inactivation is often not sufficient to initiate cancer but may still lead to some stem cell expansion, raising the possibility that strategies aimed at transiently inactivating RB might provide a novel way to expand functional stem cell populations. Future experiments dedicated to better understanding how RB and the RB pathway control a stem cell's decisions to divide, self-renew, or give rise to differentiated progeny may eventually increase our capacity to control these decisions to enhance regeneration or help prevent cancer development.
干细胞在胚胎发育和成年个体的内稳态维持中起着至关重要的作用。更好地了解干细胞生物学,包括胚胎和成人干细胞,将使科学界能够更好地理解许多病理,并可能设计出治疗各种疾病患者的新方法。视网膜母细胞瘤肿瘤抑制因子 RB 控制着细胞的增殖、分化和存活,越来越多的证据表明,RB 活性在干细胞和祖细胞的生物学中起着核心作用。在某些情况下,干细胞或祖细胞中 RB 功能的丧失是癌症起始的关键事件,并通过改变其命运来确定这些多能细胞产生的癌症亚型。在其他情况下,RB 失活通常不足以引发癌症,但仍可能导致一些干细胞扩增,这增加了一种可能性,即旨在暂时使 RB 失活的策略可能为扩大功能性干细胞群体提供一种新方法。未来专门致力于更好地了解 RB 和 RB 通路如何控制干细胞分裂、自我更新或产生分化后代的决策的实验,最终可能会提高我们控制这些决策的能力,以增强再生或帮助预防癌症的发生。