Developing a lung organoid signalome for real-time analysis of senescence-associated cellular cross talk

我们体内的细胞每天都会受到损害，尤其是肺部，因为它经常暴露在我们呼吸的空气中的危险物质中。单独来看，污染、柴油颗粒、烟草烟雾、过敏原和病毒侮辱的影响可能是轻微的，但多年重复暴露可能会导致对肺部健康产生长期影响的疾病的发展，包括特发性肺纤维化(IPF)和慢性阻塞性肺疾病(COPD)。在受到侮辱后，肺部的细胞必须决定如何做出反应。在较年轻的健康个体中，肺细胞会对轻微的侮辱做出快速修复，恢复正常的肺功能。随着我们变老，多年反复轻微损伤的影响会导致肺细胞以不同的方式做出反应，这一过程被称为细胞衰老。衰老的细胞不会分裂，所以即使是轻微的损伤，它们也不能帮助肺的修复。他们也不会死。相反，它们留在肺部，释放信号，鼓励邻近的细胞也变得衰老。这些衰老、有缺陷的细胞的积累似乎有助于慢性肺部疾病的发展，尽管确切的过程尚不清楚。我们将创建一个人类肺的3D模型，其中包含两种最重要的肺细胞类型：上皮细胞和成纤维细胞。这些细胞将被修改，以便它们可以响应衰老细胞产生的信号而改变颜色。我们将使用这个模型来尝试和了解肺部的健康细胞如何对衰老细胞发出的信号做出反应，以及邻近的细胞如何影响彼此的行为。了解衰老肺中衰老细胞的数量是如何增加的，可以帮助我们找到新的治疗方法，以防止这些功能失调的细胞聚集在肺中并导致疾病。

Cells in our body suffer damage on a daily basis, and this is particularly true in the lungs which are constantly exposed to dangerous agents in the air that we breathe. In isolation, the effect of pollution, diesel particles, tobacco smoke, allergens and viral insults may be mild, but repeated exposure over many years can lead to development of diseases which have long term effects on lung health including Idiopathic Pulmonary Fibrosis (IPF) and Chronic Obstructive Pulmonary Disease (COPD). After exposure to an insult, the cells in the lung have to decide how to respond. In younger healthy individuals, lung cells will quickly repair themselves in response to a mild insult, restoring ormal lung function. As we age, the effect of years of repeated mild injuries leads the lung cells to respond in a different way, a process called cellular senescence. Senescent cells so not divide, so they are unable to aid in the repair of the lung following even mild injury. They also do not die. Instead they remain in the lungs and release signals which encourage neighbouring cells to also become senescent. Accumulation of these senescent, defective cells appears to contribute to the development of chronic lung disease although the exact process is unclear. We will create a 3D model of the human lung which contains two of the most important lung cell types, epithelial cells and fibroblasts. These cells will be modified so that they can change colour in response to signals generated by senescent cells. We will use this model to try and understand how healthy cells in the lung respond to signals from senescent cells, and how neighbouring cells influence each other's behaviour. Understanding how senescent cells increase in number in the aging lung could help us to identify new treatment to prevent these dysfunctional cells from collecting in the lung and causing disease.