Yatabe Y, Tavaré S, Shibata D
Department of Pathology, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10839-44. doi: 10.1073/pnas.191225998. Epub 2001 Aug 21.
The stem cells that maintain human colon crypts are poorly characterized. To better determine stem cell numbers and how they divide, epigenetic patterns were used as cell fate markers. Methylation exhibits somatic inheritance and random changes that potentially record lifelong stem cell division histories as binary strings or tags in adjacent CpG sites. Methylation tag contents of individual crypts were sampled with bisulfite sequencing at three presumably neutral loci. Methylation increased with aging but varied between crypts and was mosaic within single crypts. Some crypts appeared to be quasi-clonal as they contained more unique tags than expected if crypts were maintained by single immortal stem cells. The complex epigenetic patterns were more consistent with a crypt niche model wherein multiple stem cells were present and replaced through periodic symmetric divisions. Methylation tags provide evidence that normal human crypts are long-lived, accumulate random methylation errors, and contain multiple stem cells that go through "bottlenecks" during life.
维持人类结肠隐窝的干细胞特征尚不明确。为了更好地确定干细胞数量及其分裂方式，表观遗传模式被用作细胞命运标记。甲基化具有体细胞遗传和随机变化的特点，有可能将终身干细胞分裂历史记录为相邻CpG位点的二进制字符串或标签。通过亚硫酸氢盐测序在三个可能为中性的位点对单个隐窝的甲基化标签内容进行采样。甲基化随年龄增长而增加，但在不同隐窝间存在差异，且在单个隐窝内呈镶嵌分布。一些隐窝似乎是准克隆性的，因为如果隐窝由单个永生干细胞维持，它们所含的独特标签比预期更多。复杂的表观遗传模式更符合隐窝生态位模型，即其中存在多个干细胞，并通过周期性对称分裂进行替换。甲基化标签提供了证据，表明正常人类隐窝寿命长，积累随机甲基化错误，并且含有多个在生命过程中经历“瓶颈”的干细胞。
