Identification of a key transcriptional regulator of AT1 cell development and maintenance

AT1细胞发育和维持的关键转录调节因子的鉴定

• 批准号: 9754254
• 负责人: Danielle R Little
• 金额: $ 3.2万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-04 至 2020-08-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754254
• 关键词: AGTR2 gene; Acute Lung Injury; Adoption; Adult; Affect; Alveolar; Area; Attention; Binding Sites; Blood; Breathing; Bronchopulmonary Dysplasia; Cell Maintenance; Cell Nucleus; Cell Shape; Cells; ChIP-seq; Data; Development; Diffusion; Disease; Enhancers; Epigenetic Process; Future; Gases; Genes; Genetic Models; Genetic Transcription; Genomics; Goals; Growth; Homeobox; Hyperoxia; Intestines; Investigation; Knock-out; Left; Liver; Lung; Lung diseases; Maintenance; Maps; Modeling; Morphology; Mus; Perinatal; Physiological; Pulmonary Pathology; Reporting; Role; Side; Stomach; Stream; Structure; Surface; Testing; Transcriptional Regulation; cell type; cellular imaging; experimental study; gastrointestinal; imaging modality; lung development; lung injury; mouse model; mutant; promoter; transcription factor; transcriptome sequencing

Project Summary Despite the essential role of alveolar type 1 (AT1) cells in gas exchange, the AT1 cell has not received much attention within the context of lung development, maintenance, and disease. We found that AT1 specific deletion of the transcription factor NK homeobox2.1 (NKX2.1) during development results in loss of three defining features of AT1 cells, as well as adoption of an alternative cell fate. This led to our hypothesis that NKX2.1 is a key transcriptional regulator of development and maintenance of AT1 cells. We will investigate the epigenetic mechanisms of NKX2.1 dependent transcriptional control in developing AT1 cells (aim 1) and determine the role of NKX2.1 in mature AT1 cells as well as its contribution to lung injury (aim 2). Successful completion of this study will elucidate the first transcription factors known to regulate AT1 development and maintenance, paving the way for future investigation of AT1 cells in lung development and disease. .

项目概要 尽管肺泡 1 型 (AT1) 细胞在气体交换中发挥着重要作用，但 AT1 细胞并未受到太多影响。 关注肺部发育、维护和疾病。我们发现 AT1 特有的 发育过程中转录因子 NK 同源盒2.1 (NKX2.1) 的缺失会导致三个缺失 AT1 细胞的定义特征，以及采用替代细胞命运。这导致我们的假设是 NKX2.1 是 AT1 细胞发育和维持的关键转录调节因子。我们将调查 发育中 AT1 细胞中 NKX2.1 依赖的转录控制的表观遗传机制（目标 1）和 确定 NKX2.1 在成熟 AT1 细胞中的作用及其对肺损伤的影响（目标 2）。成功的 这项研究的完成将阐明第一个已知调节 AT1 发育的转录因子 维护，为未来研究 AT1 细胞在肺部发育和疾病中的作用铺平道路。 。