Systematic dissection of gut cellular circuits [at single cell resolution]

摘要 肠道是连接和整合全身器官系统的纽带，影响深远 对健康和疾病的后果。肠道作为一个器官的生物功能是复杂的结果 动态和异质细胞类型之间的相互作用。对肠道的任何病理性侮辱，如屏障 违规或感染，必须得到与侮辱适当和成比例的回应，以便 动态平衡重新建立起来。在这个应用中，我们提出了新的单细胞基因组方法来 破译异质细胞对炎症挑战的反应。通过一系列功能遗传学 本研究旨在从病理学的角度阐明粘膜免疫的分子基础。 发炎。为此，我们提出以下具体目标： 目的1.全面定义肠道炎症中的所有细胞系和动态功能状态。 目的2.描绘协调肠道炎症的细胞间通讯网络。 目标3：在人类活检组织中识别疾病修饰物通路，并与细胞间通讯相结合 网络。

ABSTRACT The gut serves as a nexus that connects and integrates organ systems throughout the body, with far-reaching consequences in health and disease. The biological function of the gut as an organ is the result of complex interactions between dynamic and heterogeneous cell types. Any pathological insult to the gut, such as barrier breach or infection, must be met with a response that is appropriate and proportional to the insult, such that homeostasis is re-established. In this application, we propose novel single-cell genomic approaches to decipher heterogeneous cellular responses to inflammatory challenge. Through a series of functional genetics studies, we aim to elucidate the molecular basis of mucosal immunity in the context of pathological inflammation. Towards this end, we propose the following specific aims: Aim 1. Comprehensively define all cell lineages and dynamic functional states in intestinal inflammation. Aim 2. Delineate intercellular communication networks that coordinate intestinal inflammation. Aim 3. Identify disease modifier pathways in human biopsies and integrate with intercellular communication networks.