Department of Molecular & Cellular Physiology and Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Foldscope Instruments, Inc., Palo Alto, CA, USA.
Nat Cell Biol. 2023 May;25(5):658-671. doi: 10.1038/s41556-023-01116-w. Epub 2023 Mar 30.
Barrier epithelial organs face the constant challenge of sealing the interior body from the external environment while simultaneously replacing the cells that contact this environment. New replacement cells-the progeny of basal stem cells-are born without barrier-forming structures such as a specialized apical membrane and occluding junctions. Here, we investigate how new progeny acquire barrier structures as they integrate into the intestinal epithelium of adult Drosophila. We find they gestate their future apical membrane in a sublumenal niche created by a transitional occluding junction that envelops the differentiating cell and enables it to form a deep, microvilli-lined apical pit. The transitional junction seals the pit from the intestinal lumen until differentiation-driven, basal-to-apical remodelling of the niche opens the pit and integrates the now-mature cell into the barrier. By coordinating junctional remodelling with terminal differentiation, stem cell progeny integrate into a functional, adult epithelium without jeopardizing barrier integrity.
屏障上皮器官面临着将内部身体与外部环境隔离的持续挑战,同时还要替换与该环境接触的细胞。新的替代细胞——基底干细胞的后代——在没有形成屏障的结构(如专门的顶膜和封闭连接)的情况下产生。在这里,我们研究了新的后代在整合到成年果蝇的肠道上皮时如何获得屏障结构。我们发现,它们在一个由过渡性封闭连接形成的亚腔室中孕育未来的顶膜,这个连接包围着正在分化的细胞,使它能够形成一个深的、微绒毛状的顶坑。过渡连接将坑与肠道腔室隔离,直到由分化驱动的、基底到顶的龛位重塑打开坑,并将现在成熟的细胞整合到屏障中。通过协调连接的重塑和终端分化,干细胞后代整合到一个功能齐全的成年上皮中,而不会危及屏障的完整性。