Cell-cell interactions governing lung epithelial progenitor cells

细胞间相互作用控制肺上皮祖细胞

• 批准号: 9902712
• 负责人: Carla F. Kim
• 金额: $ 88.5万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2027-01-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9902712
• 关键词: 3-Dimensional; Adult; Alveolar; Biological Assay; Biological Process; Biology; Cataloging; Catalogs; Cell Communication; Cells; Coculture Techniques; Communities; Development; Endothelial Cells; Environment; Epithelial; Epithelium; Focus Groups; Homeostasis; Human; Lung; Lung diseases; Malignant neoplasm of lung; Mesenchymal; Methods; Modeling; Molecular; Organoids; Regenerative Medicine; Research; Role; Signal Transduction; Stem cell transplant; Structure; Structure of parenchyma of lung; Supporting Cell; System; Techniques; Therapeutic Intervention; Therapeutic Uses; Transplantation; cell type; epithelial stem cell; injury and repair; lung injury; mouse model; novel strategies; paracrine; progenitor; programs; repaired; response to injury; single-cell RNA sequencing; stem cell biology; stem cells; tool

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.

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