Investigating stem cells in human colon by using methylation patterns
Investigating stem cells in human colon by using methylation patterns
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DOI：
10.1073/pnas.191225998
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发表时间：
2001-09-11
影响因子：
11.1
通讯作者：
Shibata, D
中科院分区：
文献类型：
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作者：
Yatabe, Y;Tavaré, S;Shibata, D
维持人类结肠隐窝的干细胞的特征很差。为了更好地确定干细胞数量和它们如何分裂，表观遗传模式被用作细胞命运标记。甲基化表现出体细胞遗传和随机变化，可能记录终身干细胞分裂的历史作为二进制字符串或标签在相邻的CpG位点。甲基化标签内容的个别隐窝取样与亚硫酸氢盐测序在三个假定中性位点。甲基化随着年龄的增长而增加，但不同的隐窝和镶嵌在单一的隐窝。一些隐窝似乎是准克隆的，因为如果隐窝由单个永生干细胞维持，则它们含有比预期更多的独特标签。复杂的表观遗传模式更符合隐窝小生境模型，其中存在多个干细胞并通过周期性对称分裂进行替换。甲基化标签提供的证据表明，正常的人类隐窝是长寿的，积累随机甲基化错误，并包含多个干细胞，在生活中经历“瓶颈”。
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 quarsi-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.