Cell-cell interactions governing lung epithelial progenitor cells

摘要 我的实验室的贡献帮助将肺生物学带入了干细胞生物学的前沿。我们的主要关注点是 一直在开发工具来表征成人肺和肺癌中的祖细胞；我现在的目标是开发 这一专业知识在肺部疾病中的应用。我们创造了三维共培养有机体系统 已经开始定义上皮祖细胞和其他支持细胞类型之间的细胞-细胞串扰 肺部。我们现在可以模拟由肺祖细胞形成的呼吸道和肺泡样结构， 我们有一个在分子水平上了解分化控制的平台。这项研究计划 寻求在我们的进展的基础上进一步开发肺器官类物质来审问分子 成人肺上皮祖细胞与其环境之间细胞-细胞相互作用的基础 动态平衡和病变肺中。我们将确定上皮祖细胞通过哪些信号 在肺损伤反应和修复过程中受间充质细胞和内皮细胞的调节。单元格来自 肺部疾病的小鼠模型将被用于单细胞RNA测序和在器官系统中识别 可用于治疗干预的细胞自主和旁分泌机制。我们将完善我们的 用于人类肺细胞的技术。我们将创建一种肺祖细胞移植试验，一种关键的 肺脏需要研究祖细胞和再生医学。而其他团体则是 专注于对肺细胞类型的分类，我们的策略将提供必要的工具来审问生物学 不同肺细胞的功能。总的来说，这些新方法将使我们能够继续建立和利用 探索正常肺和肺部疾病生物学的许多方面的变革性方法。

Summary My lab’s contributions have helped bring lung biology to the forefront of stem cell biology. Our major focus has been to develop tools to characterize progenitor cells in the adult lung and in lung cancer; I now aim to develop this expertise for applications in lung diseases. We created three-dimensional co-culture organoid systems that have begun to define cell-cell crosstalk between epithelial progenitors and other supporting cell types in the lung. We can now model the formation of airway- and alveolar-like structures from lung progenitor cells, and we have a platform to understand differentiation control at the molecular level. This research program seeks to build on our advances and to further develop lung organoids to interrogate the molecular underpinnings of cell-cell interactions between epithelial progenitor cells and their environment in the adult lung homeostasis and in diseased lung. We will determine the signals through which epithelial progenitors are regulated by mesenchymal cells and endothelial cells during lung injury response and repair. Cells from mouse models of lung disease will be used for single cell RNA-sequencing and in organoid systems to identify cell autonomous and paracrine mechanisms that can be used for therapeutic intervention. We will refine our techniques for use with human lung cells. We will create a lung progenitor cell transplantation assay, a critical need in the lung community for the study of progenitors and for regenerative medicine. While other groups are focused on cataloging lung cell types, our strategies will provide essential tools to interrogate the biological functions of diverse lung cells. Collectively, these new approaches will allow us to continue to build and utilize transformative methods to probe numerous aspects of the biology of normal lung and lung disease.