Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.
PLoS One. 2012;7(6):e38965. doi: 10.1371/journal.pone.0038965. Epub 2012 Jun 20.
Adult stem cell niches are often co-inhabited by cycling and quiescent stem cells. In the intestine, lineage tracing has identified Lgr5(+) cells as frequently cycling stem cells, whereas Bmi1(+), mTert(+), Hopx(+) and Lrig1(+) cells appear to be more quiescent. Here, we have applied a non-mutagenic and cell cycle independent approach to isolate and characterize small intestinal label-retaining cells (LRCs) persisting in the lower third of the crypt of Lieberkühn for up to 100 days. LRCs do not express markers of proliferation and of enterocyte, goblet or enteroendocrine differentiation, but are positive for Paneth cell markers. While during homeostasis, LR/Paneth cells appear to play a supportive role for Lgr5(+) stem cells as previously shown, upon tissue injury they switch to a proliferating state and in the process activate Bmi1 expression while silencing Paneth-specific genes. Hence, they are likely to contribute to the regenerative process following tissue insults such as chronic inflammation.
成人干细胞龛通常由循环和静止的干细胞共同占据。在肠道中，谱系追踪已经确定 Lgr5(+)细胞是经常循环的干细胞，而 Bmi1(+)、mTert(+)、Hopx(+)和 Lrig1(+)细胞似乎更静止。在这里，我们应用了一种非突变和细胞周期独立的方法来分离和鉴定在 Lieberkühn 隐窝底部持续存在长达 100 天的小肠标记保留细胞 (LRC)。LRC 不表达增殖和肠细胞、杯状细胞或肠内分泌分化的标志物，但对 Paneth 细胞标志物呈阳性。虽然在体内平衡时，LR/Paneth 细胞似乎如前所述为 Lgr5(+)干细胞提供支持作用，但在组织损伤时，它们会转变为增殖状态，并在此过程中激活 Bmi1 表达，同时沉默 Paneth 特异性基因。因此，它们可能有助于组织损伤（如慢性炎症）后的再生过程。
