荷兰癌症研究所Jacco van Rheenen、奥地利科学技术研究所Edouard Hannezo、瑞典卡罗林斯卡学院Pekka Katajisto和英国剑桥大学Benjamin D. Simons团队合作取得一项新突破。他们的最新研究发现小肠干细胞的逆行运动决定肠内有效干细胞的数量。相关论文于2022年7月13日发表在《自然》杂志上。

研究人员使用活体显微镜发现尽管小鼠中具有Lgr5特征增殖细胞的数量和分布相似，但小肠隐窝中有效干细胞的数量是大肠隐窝的两倍。研究发现，虽然以传送带状向上被动移位，但由于Wnt依赖性逆行细胞运动，远离隐窝底部的小肠细胞可以作为长期有效干细胞发挥功能。相比之下，大肠中的干细胞几乎没有逆行运动从而限制了细胞重新定位，导致有效干细胞数量减少。而且，抑制小肠逆行运动后，有效干细胞数量减少，隐窝单克隆转化率加快。

总之，这些结果表明，有效干细胞的数量是由主动逆行运动决定的，从而揭示了一种可以通过实验和药物对干细胞进行调节的新通道。

据介绍，肠道上皮细胞的形态和功能各不相同，但所有部位组织的更新都是由隐窝底部干细胞诱导的。尚不清楚不同部位干细胞的数量和行为是否不同。

附：英文原文

Title: Retrograde movements determine effective stem cell numbers in the intestine

Author: Azkanaz, Maria, Corominas-Murtra, Bernat, Ellenbroek, Saskia I. J., Bruens, Lotte, Webb, Anna T., Laskaris, Dimitrios, Oost, Koen C., Lafirenze, Simona J. A., Annusver, Karl, Messal, Hendrik A., Iqbal, Sharif, Flanagan, Dustin J., Huels, David J., Rojas-Rodrguez, Felipe, Vizoso, Miguel, Kasper, Maria, Sansom, Owen J., Snippert, Hugo J., Liberali, Prisca, Simons, Benjamin D., Katajisto, Pekka, Hannezo, Edouard, van Rheenen, Jacco

Issue&Volume: 2022-07-13

Abstract: The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts1,2,3. Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated.

DOI: 10.1038/s41586-022-04962-0

Source: https://www.nature.com/articles/s41586-022-04962-0