Esophageal progenitor cell plasticity; a 3D organotypic model of epithelial regeneration [scATAC-seq]

Epithelial stem cells are capable of remarkable plasticity, facilitating efficient regenerative responses following damage. Here, we present a versatile model of ectopic niche regeneration that provides evidence of a switch in epithelial stem cell identity as a response to foreign microenvironmental signals. A combination of 3D organotypic cultures, 3D confocal imaging and Next-Generation Sequencing reveal events of epithelial plasticity during the reepithelialization of denuded stroma. In this study we provide new insights on the mechanisms driving cell fate flexibility in adult epithelial stem cells. Single-cell ATAC sequencing of murine esophageal epithelial cells, cultured in a 3D organotypic system that recapitulates wound healing. Cells growing over their native stroma (eEE) were compared to those growing over the foreign stroma of the dermis (eSKIN).

上皮干细胞（epithelial stem cells）具备显著的可塑性，可在组织损伤后介导高效的再生修复反应。本研究构建了一种可用于异位干细胞龛再生的通用模型，为上皮干细胞身份在外源微环境信号刺激下发生转换提供了实验依据。本研究通过三维器官型培养、三维共聚焦成像与下一代测序（Next-Generation Sequencing）的联合分析，揭示了裸露间质创面再上皮化过程中上皮可塑性的相关事件。本研究为解析成体上皮干细胞的细胞命运灵活性调控机制提供了全新见解。本研究对在模拟伤口愈合过程的三维器官型培养体系中培养的小鼠食管上皮细胞开展了单细胞ATAC测序（single-cell ATAC sequencing）。研究将在自身原生间质上生长的细胞（eEE）与在异体真皮间质上生长的细胞（eSKIN）进行了对照比较。