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

项目摘要 尽管肺泡I型(AT1)细胞在气体交换中起着重要作用，但AT1细胞并没有收到太多 在肺发育、维护和疾病的背景下注意。我们发现AT1特异性 转录因子NK Homeobox2.1(Nkx2.1)在发育过程中的缺失导致三个 确定AT1细胞的特征，以及采用另一种细胞命运。这导致了我们的假设 Nkx2.1是AT1细胞发育和维持的关键转录调控因子。我们将调查 发育中AT1细胞中Nkx2.1依赖转录调控的表观遗传学机制(Aim 1)和 确定Nkx2.1在成熟AT1细胞中的作用及其对肺损伤的贡献(目标2)。成功 这项研究的完成将阐明已知的第一个调控AT1发育和 维护，为未来研究AT1细胞在肺发育和疾病中的作用铺平了道路。 。

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. .