美国斯坦福大学医学院Lucy Erin O’Brien课题组近日取得一项新成果。经过不懈努力，他们发现在成体上皮细胞交接生态位连接处基底干细胞子代建立其顶端表层。相关论文于2023年3月30日发表于国际学术期刊《自然-细胞生物学》杂志。

研究人员揭示了在整合到成年果蝇肠上皮时新生子代细胞如何获得屏障结构。研究发现它们在由过渡闭塞连接产生的管腔下壁生态位中形成未来的顶膜结构，该连接包住分化细胞并使其形成一个深的微绒毛衬里顶端凹坑。过渡连接将凹坑与肠腔密封，直到分化驱动的基底-顶端重塑生态位打开凹坑并将现已成熟的细胞整合到屏障中。通过协调连接重塑与终末分化，干细胞后代整合到功能性的成体上皮中且不会损害屏障完整性。

研究人员表示，屏障上皮器官面临着许多挑战，既要使内部细胞与外部环境隔离，同时又要更换与该环境接触的细胞。新生替代细胞（基底干细胞的后代）产生时并没有形成屏障结构，例如专门的顶膜和闭塞连接。

附：英文原文

Title: Basal stem cell progeny establish their apical surface in a junctional niche during turnover of an adult barrier epithelium

Author: Galenza, Anthony, Moreno-Roman, Paola, Su, Yu-Han, Acosta-Alvarez, Lehi, Debec, Alain, Guichet, Antoine, Knapp, Jon-Michael, Kizilyaprak, Caroline, Humbel, Bruno M., Kolotuev, Irina, OBrien, Lucy Erin

Issue&Volume: 2023-03-30

Abstract: 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.

DOI: 10.1038/s41556-023-01116-w

Source: https://www.nature.com/articles/s41556-023-01116-w