Department of Biomedical Sciences, School of Veterinary Medicine and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stowers Institute for Medical Research, Kansas City, Missouri, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66101, USA.
Trends Cell Biol. 2017 Oct;27(10):753-764. doi: 10.1016/j.tcb.2017.06.006. Epub 2017 Jul 18.
Somatic stem cells maintain tissue homeostasis by organizing themselves in such a way that they can maintain proliferative output while simultaneously protecting themselves from DNA damage that may lead to oncogenic transformation. There is considerable debate about how such stem cell compartments are organized. Burgeoning evidence from the small intestine and colon provides support for a two-stem cell model involving an actively proliferating but injury-sensitive stem cell and a rare, injury-resistant pool of quiescent stem cells. Parallel with this evidence, recent studies have revealed considerable plasticity within the intestinal stem cell (ISC) compartment. We discuss the evidence for plasticity and hierarchy within the ISC compartment and how these properties govern tissue regeneration and contribute to oncogenic transformation leading to colorectal cancers.
体细胞干细胞通过自我组织的方式维持组织内稳态,从而既能保持增殖输出,又能保护自身免受可能导致致癌转化的 DNA 损伤。关于如何组织这些干细胞隔室存在相当大的争议。来自小肠和结肠的大量新证据支持涉及活跃增殖但易受伤的干细胞和罕见的、静止的抗损伤干细胞池的两干细胞模型。与这一证据平行的是,最近的研究揭示了肠道干细胞(ISC)隔室中相当大的可塑性。我们讨论了 ISC 隔室中可塑性和层次结构的证据,以及这些特性如何控制组织再生并促进导致结直肠癌的致癌转化。