Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells
Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells
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DOI：
10.1073/pnas.1013004108
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发表时间：
2011-01-04
影响因子：
11.1
通讯作者：
Breault, David T.
中科院分区：
文献类型：
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作者：
Montgomery, Robert K.;Carlone, Diana L.;Breault, David T.
肠上皮由快速循环（Lgr 5（+））肠干细胞（ISCs）群体维持。然而，据推测，缓慢循环的ISC也必须存在于肠中以保护基因组免于积累有害突变并允许对组织损伤的反应。在这里，我们确定了一个亚群的缓慢循环的ISCs标记的小鼠端粒酶逆转录酶（mTert）的表达，可以产生Lgr 5（+）细胞。表达mTert的细胞以类似于长期标记保留细胞（LRC）的模式沿着隐窝-绒毛轴分布，并且对组织损伤具有抗性。谱系追踪研究表明，mTert（+）细胞产生所有分化的肠细胞类型，长期存在，并有助于损伤后的再生反应。与其他高度再生的组织一致，我们的研究结果表明，肠道内存在缓慢循环的干细胞群。
The intestinal epithelium is maintained by a population of rapidly cycling (Lgr5(+)) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5(+) cells. mTert-expressing cells distribute in a pattern along the crypt-villus axis similar to long-term label-retaining cells (LRCs) and are resistant to tissue injury. Lineage-tracing studies demonstrate that mTert(+) cells give rise to all differentiated intestinal cell types, persist long term, and contribute to the regenerative response following injury. Consistent with other highly regenerative tissues, our results demonstrate that a slowly cycling stem cell population exists within the intestine.