Stem cells: the intestinal stem cell as a paradigm
Stem cells: the intestinal stem cell as a paradigm
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DOI：
10.1093/carcin/21.3.469
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发表时间：
2000-03-01
期刊：
影响因子：
4.7
通讯作者：
Potten, CS
中科院分区：
文献类型：
--
作者：
Bach, SP;Renehan, AG;Potten, CS
干细胞研究为肿瘤学、临床遗传学和各种退行性疾病的治疗进展提供了基础。例如，阐明细胞系统内控制增殖调节和分化的途径将导致针对癌症根本原因的医学策略。目前，可靠的干细胞标记物的表征是这一特定领域的直接目标。在过去的30年里，研究人员已经通过仔细和富有想象力的实验确定了干细胞的许多物理和功能特性。肠干细胞位于隐窝基部，并产生隐窝内发现的所有细胞类型。他们很容易经历利他性细胞凋亡，以应对有毒的刺激，虽然他们的后代是耐寒，并将重新获得干细胞功能，重新填充组织隔室，从而产生了增殖层次的概念。当决定一个隐窝内的全部细胞是来自单个干细胞还是多个干细胞时，存在竞争。也有证据挑战长期持有的观点，即结直肠肿瘤是由单个突变的干细胞引起的，因为来自人XO/XY嵌合体的早期腺瘤包含不同的克隆，支配干细胞周期和随后的增殖活性的机制在很大程度上仍然不清楚。然而，腺瘤性结肠息肉病基因产物已显示促进β-连环蛋白（细胞增殖的增强剂）的降解，从而下调健康个体中的这种活性。
Stem cell research provides a foundation for therapeutic advancement in oncology, clinical genetics and a diverse array of degenerative disorders. For example, the elucidation of pathways governing proliferative regulation and differentiation within cellular systems mill result in medical strategies aimed at the root cause of cancer. At present the characterization of reliable stem cell markers is the immediate aim in this particular field. Over the past 30 years investigators have determined many of the physical and functional properties of stem cells through careful and imaginative experimentation. Intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt. They readily undergo altruistic apoptosis in response to toxic stimuli although their progeny are hardier and will regain stem cell function to repopulate the tissue compartment, giving rise to the concept of a proliferative hierarchy. Contention exists when deciding whether the full complement of cells within a crypt is derived from either a single or multiple stems. Evidence has also arisen to challenge the long held view that colorectal tumours arise from a single mutated stem cell, as early adenomas from a human XO/XY mosaic contained distinct clones, Mechanisms governing the stem cell cycle and subsequent proliferative activity largely remain obscure. The adenomatous polyposis coli gene product has, however, been shown to promote the degradation of beta-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.