Bmi1 is expressed in vivo in intestinal stem cells
Bmi1 is expressed in vivo in intestinal stem cells
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DOI：
10.1038/ng.165
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发表时间：
2008-07-01
期刊：
影响因子：
30.8
通讯作者：
Capecchi, Mario R.
中科院分区：
文献类型：
--
作者：
Sangiorgi, Eugenio;Capecchi, Mario R.
Bmi1在造血干细胞和神经干细胞的自我更新中起着至关重要的作用。为了研究它在其他成体干细胞群体中的作用，我们培育了一种在Bmi1基因座表达他莫昔芬诱导型Cre的小鼠。我们发现Bmi1在小肠隐窝底部附近的特定细胞中表达，主要是在隐窝底部上方四个细胞的位置（+4位置）。随着时间的推移，这些细胞增殖、扩增、自我更新，并产生小肠上皮的所有分化细胞谱系。在这些细胞中诱导稳定形式的β-连环蛋白足以快速产生腺瘤。此外，使用表达白喉毒素的Rosa26条件性等位基因消融Bmi1+细胞会导致隐窝丢失。这些实验确定Bmi1是体内肠道干细胞的标志物。出乎意料的是，表达Bmi1的干细胞在小肠长度方向上的分布表明，哺乳动物使用不止一种在分子上可区分的成体干细胞亚群来维持器官内稳态。
Bmi1 plays an essential part in the self-renewal of hematopoietic and neural stem cells. To investigate its role in other adult stem cell populations, we generated a mouse expressing a tamoxifen-inducible Cre from the Bmi1 locus. We found that Bmi1 is expressed in discrete cells located near the bottom of crypts in the small intestine, predominantly four cells above the base of the crypt (+4 position). Over time, these cells proliferate, expand, self-renew and give rise to all the differentiated cell lineages of the small intestine epithelium. The induction of a stable form of beta-catenin in these cells was sufficient to rapidly generate adenomas. Moreover, ablation of Bmi1+ cells using a Rosa26 conditional allele, expressing diphtheria toxin, led to crypt loss. These experiments identify Bmi1 as an intestinal stem cell marker in vivo. Unexpectedly, the distribution of Bmi1-expressing stem cells along the length of the small intestine suggested that mammals use more than one molecularly distinguishable adult stem cell subpopulation to maintain organ homeostasis.