Apoptosis Differently Affects Lineage Tracing of Lgr5 and Bmi1 Intestinal Stem Cell Populations
Apoptosis Differently Affects Lineage Tracing of Lgr5 and Bmi1 Intestinal Stem Cell Populations
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DOI：
10.1016/j.stem.2013.01.003
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发表时间：
2013-03-07
期刊：
影响因子：
23.9
通讯作者：
Bulavin, Dmitry V.
中科院分区：
文献类型：
--
作者：
Zhu, Yunhua;Huang, Yi-Fu;Bulavin, Dmitry V.
新出现的谱系追踪数据支持成年小鼠中存在几个肠道干细胞(ISCs)池。已知+4位置含有对辐射反应发生强烈凋亡的增殖细胞，但它们与最近报道的ISC模型的关系尚不清楚。在这里，我们发现他莫昔芬，在通常用于诱导谱系追踪的剂量，模拟辐射诱导的+4细胞的凋亡反应。我们发现大约40%的凋亡细胞是Lgr5阳性的，而Bmi1阳性的ISCs在进入增殖状态时对他莫昔芬变得敏感。反过来，当我们通过Bcl2过表达或Chk2缺失来抑制细胞凋亡时，我们发现Lgr5阳性细胞的谱系追踪有效地减少了。相反，在缺乏细胞凋亡的背景下，来自Bmi1阳性的ISCs的谱系追踪显著增加。我们认为，细胞凋亡在控制小鼠肠道中不同ISC群体的谱系追踪中起着重要作用。
Emerging lineage-tracing data support the existence of several pools of intestinal stem cells (ISCs) in the adult mouse. The +4 location is known to harbor proliferative cells undergoing robust apoptosis in response to irradiation, but their relationship with recently reported ISC models is unclear. Here, we found that tamoxifen, at doses commonly used to induce lineage tracing, mimics the irradiation-induced apoptotic response of the +4 cells. We found that about 40% of apoptotic cells were Lgr5-positive whereas Bmi1-positive ISCs became sensitive to tamoxifen upon entering a proliferative state. In turn, when we suppressed apoptosis by either Bcl2 overexpression or Chk2 deletion, we found that lineage tracing of Lgr5-positive cells was efficiently reduced. In contrast, lineage tracing from Bmi1-positive ISCs was substantially increased in apoptosis-deficient backgrounds. We propose that apoptosis plays an important role in controlling lineage tracing from different ISC populations in the mouse intestine.