Potten C S
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Philos Trans R Soc Lond B Biol Sci. 1998 Jun 29;353(1370):821-30. doi: 10.1098/rstb.1998.0246.
The mammalian intestinal mucosa, with its distinctive polarity, high rate of proliferation and rapid cell migration, is an excellent model system to study proliferative hierarchies and the regulation of cell division, differentiation and cell death. Each crypt contains a few lineage ancestral stem cells (the 'ultimate stem cells'). However, there are other potential stem cells within the early lineage, and many rapidly proliferating transit cells with no stem cell capabilities. Apoptosis under two circumstances has a specificity for the ultimate stem cells in the small intestine and this represents, in one case, part of the stem cell homeostatic process and, in another case, a protective mechanism against DNA damage. Apoptosis occurs with a lower frequency in the large intestine owing to the expression of the bcl-2 gene in this region, and this probably contributes to the causes for the low cancer risk in the small bowel and the high risk in the large bowel. Current studies are beginning to unravel the complex interaction of growth factors and regulatory genes that determine whether a cell divides, differentiates or dies.
哺乳动物的肠道黏膜具有独特的极性、高增殖率和快速的细胞迁移能力，是研究增殖层次以及细胞分裂、分化和细胞死亡调控的极佳模型系统。每个隐窝含有少数谱系祖干细胞（“终极干细胞”）。然而，在早期谱系中还存在其他潜在干细胞，以及许多没有干细胞能力的快速增殖的过渡细胞。在两种情况下，细胞凋亡对小肠中的终极干细胞具有特异性，在一种情况下，这是干细胞稳态过程的一部分，在另一种情况下，是一种针对DNA损伤的保护机制。由于该区域bcl-2基因的表达，细胞凋亡在大肠中发生的频率较低，这可能是导致小肠癌症风险低而大肠癌症风险高的原因之一。目前的研究开始揭示决定细胞是分裂、分化还是死亡的生长因子和调控基因之间的复杂相互作用。
