REGULATION OF ALVEOLAR EPITHELIAL CELL DIFFERENTIATION

肺泡上皮细胞分化的调节

• 批准号: 2223356
• 负责人: Jerome S Brody
• 金额: $ 142.57万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-21 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2223356
• 关键词: cell differentiation; epithelium; gene expression; genetic regulation; lung alveolus

This Program Project Grant is concerned with the developmental biology of the lung. It deals with an important but poorly understood area of lung biology related to regulation of differentiation of alveolar epithelial cells during embryonic, fetal and early postnatal life. We will apply a broad panel of markers for the differentiated phenotypes of alveolar type 1 and type 2 cells that we have developed or are characterizing in our laboratories, to multidisciplinary studies which examine the transcriptional and translational regulation of expression of these differentiation-related genes at organ, cellular and molecular levels. Our experimental systems include embryonic and fetal lungs, isolated lung epithelial cells, molecules and genes. Our ungoing studies of lung development have raised questions about existing concepts of alveolar epithelial cell differentiation and have allowed us to pose a number of new hypotheses regarding timing, lineages, and regulatory mechanisms of alveolar epithelial cell differentiation. The proposal involves a number of investigators who have been working in developmental biology of the lung for some time and adds investigators with experience in other model systems of development. The program consists of four focused projects which are designed to be highly interactive, supported by two scientific and an administrative core. Project I focuses on timing and spatial patterns of gene expression in embryonic and fetal lung and analysis of factors which may modulate this process. Project II, using isolated fetal lung epithelial cells and two immortalized type 2 cell lines developed in our laboratories, examines biologic and molecular mechanisms which regulate expression of the above panel of genes. Projects III deals with molecular regulation of expression of several genes identified in proliferation-arrested type 2 cells and examines mechanisms of proliferation arrest in these cells. Project IV will utilize the embryonic lung to investigate epithelial cell lineage. the process of cell determination and the expression of genes which may effect the positional patterns of cell differentiation studied in Project I. The work proposed will provide new concepts of alveolar epithelial cell differentiation and new information of the regulation of gene expression and functions of the cells which form the gas exchange surface of the lung.

该计划项目资助关注的是发育生物学 肺 它涉及肺的一个重要但知之甚少的区域 与肺泡上皮细胞分化调节相关的生物学 胚胎、胎儿和出生后早期的细胞。 我们将采用 肺泡型分化表型的一组广泛的标记物 1型和2型细胞，我们已经开发或正在表征我们的 实验室，到检查 转录和翻译调节这些表达 分化相关基因在器官、细胞和分子水平上的表达。 我们的实验系统包括胚胎和胎儿肺、离体肺 上皮细胞、分子和基因。 我们正在进行的肺部研究 发展提出了关于肺泡的现有概念的问题， 上皮细胞分化，使我们能够提出一些 关于时间，血统和调节机制的新假设， 肺泡上皮细胞分化 该提案涉及一些 研究者们一直致力于发展生物学， 并增加了具有其他模型经验的研究者 发展系统。 该计划包括四个重点项目 这是一个高度互动的设计，由两个科学的支持， 一个行政核心。 项目一侧重于时间和空间 胚胎和胎儿肺组织基因表达谱及相关基因分析 这些因素可能会影响这一过程。 项目二，使用隔离 胎肺上皮细胞和两个永生化2型细胞系 在我们的实验室中开发，检查生物和分子机制， 其调节上述基因组的表达。 项目三 涉及几个基因表达的分子调控 在增殖停滞的2型细胞中， 这些细胞中的增殖停滞。 项目四将利用 胚胎肺研究上皮细胞谱系。的过程 细胞决定和基因的表达，可能会影响 在项目I中研究的细胞分化的位置模式。的 这项工作将为肺泡上皮细胞提供新的概念， 分化和基因表达调控的新信息 以及形成气体交换表面的细胞的功能 肺。