文章：

干细胞动态在体内平衡和肠癌

Stem cell dynamics in homeostasis and cancer of the intestine

原文发布日期：2014-06-12

DOI: 10.1038/nrc3744

类型: Review Article

开放获取: 否

要点：

1. Intestinal stem cells (ISCs) are not static entities but are instead involved in many dynamical processes.
2. ISCs are equipotent and continuously replace each other in neutral events.
3. The ISC phenotype is the sum of all markers and features that are commonly associated with stem cells in the intestine. Therefore, the ISC phenotype is continuously changing as new markers and features are being identified.
4. ISC activity is the ability of cells to initiate clonal long-term, multipotent lineages and is typically assessed by lineage tracing experiments.
5. ISC potential refers to the display of ISC activity solely in a specific context but not during homeostasis; for example, during regeneration after tissue injury. Examples of intestinal cells with ISC potential are label-retaining Paneth cell precursors and Delta-like 1-positive (DLL1⁺) secretory precursors.
6. The functional ISC compartment is the number of cells with ISC activity corrected for their relative contribution to the total output of the stem cell compartment.
7. Mutations that are commonly found in colorectal cancer (CRC), such as adenomatous polyposis coli (APC) inactivation and KRAS activation, act on ISC dynamics and give a competitive advantage to the cell in which they occur.
8. The benefit of mutated ISCs over wild-type ISCs is not absolute, and mutated ISCs are frequently outcompeted by wild-type ISCs.
9. CRCs contain cells with stem cell-like activity; however, the frequency of these cells remains unknown, as does the importance of these cells for the biology of CRCs.
10. Differentiated cancer cells and cancer stem cells are in constant flux, which is influenced by signals that emanate from the tumour stroma.

要点翻译：

1. 肠道干细胞并非静态实体，而是参与诸多动态过程。
2. 肠道干细胞具有多能性，并在中性事件中持续相互替代。
3. 肠道干细胞表型是肠道中通常与干细胞相关的所有标记物和特征的总和。因此，随着新标记物和特征的不断发现，肠道干细胞表型也在持续演变。
4. 肠道干细胞活性指细胞启动克隆性长期多能谱系的能力，通常通过谱系追踪实验进行评估。
5. 肠道干细胞潜能指仅在特定情境（如组织损伤后的再生过程）中展现干细胞活性，而在稳态条件下不显现的能力。具有此类潜能的肠道细胞包括标记滞留型潘氏细胞前体和Delta样1蛋白阳性分泌前体。
6. 功能性肠道干细胞区群指具有干细胞活性的细胞数量，并根据其对干细胞区群总输出的相对贡献进行校正。
7. 结直肠癌常见突变（如腺瘤性结肠息肉病基因失活和KRAS激活）作用于肠道干细胞动力学，并使发生突变的细胞获得竞争优势。
8. 突变型肠道干细胞的优势并非绝对，其常被野生型肠道干细胞淘汰。
9. 结直肠癌包含具有类干细胞活性的细胞，但这些细胞的频率及其对结直肠癌生物学的重要性仍属未知。
10. 分化型癌细胞与癌症干细胞处于持续动态平衡中，这一过程受到肿瘤基质信号的调节。

英文摘要：

Intestinal stem cells (ISCs) and colorectal cancer (CRC) biology are tightly linked in many aspects. It is generally thought that ISCs are the cells of origin for a large proportion of CRCs and crucial ISC-associated signalling pathways are often affected in CRCs. Moreover, CRCs are thought to retain a cellular hierarchy that is reminiscent of the intestinal epithelium. Recent studies offer quantitative insights into the dynamics of ISC behaviour that govern homeostasis and thereby provide the necessary baseline parameters to begin to apply these analyses during the various stages of tumour development.

摘要翻译： 

肠道干细胞（ISC）与结直肠癌（CRC）生物学在多个方面紧密相关。普遍认为，ISC是大多数CRC的起源细胞，且与ISC相关的关键信号通路在CRC中常受影响。此外，CRC被认为保留了类似肠道上皮的细胞层级结构。最新研究定量揭示了维持稳态的ISC行为动态，从而为在肿瘤发展各阶段应用这些分析提供了必要的基线参数。

原文链接：

Stem cell dynamics in homeostasis and cancer of the intestine