Decode the Impact of SARS-CoV-2 on Human Pancreas

抽象的。 最近的临床数据表明，冠状病毒疾病19（COVID-19）和 糖尿病 患有糖尿病和严重肥胖的人更有可能 并发症，并有较高的COVID-19 死亡率 症状性 .相反，新发糖尿病和严重 的风险更高， 已在COVID-19患者中观察到既存糖尿病的代谢并发症。因此，有一个 强烈需要了解COVID-19患者胰腺功能障碍的病理和机制。在这里， 我们证明了在COVID-19尸检样本的胰腺内分泌细胞中检测到SARS-CoV-2 患者单细胞RNA-seq和免疫染色证实，多种类型的胰岛细胞是 对SARS-CoV-2易感，引发细胞应激反应和诱导趋化因子。在SARS期间- CoV-2感染后，β细胞显示胰岛素表达减少，α和β细胞表达增加。 腺泡细胞标志物，分别包括胰高血糖素和PRSS 1/胰蛋白酶1，提示细胞 转分化 尸检标本致病性检验的自动化技术 COVID-19患者。此外，我们将使用人类胰岛和血管化的人类胰腺类器官 系统评价直接感染和旁分泌炎症信号在人类 内分泌细胞的细胞特性、功能和存活。 在提案中，我们将采用最先进的 通过这项研究，我们希望提供一个 系统概述了COVID-19患者胰腺的病理变化，并详细介绍了 了解内分泌细胞功能障碍的机制，这将为开发新的 保护COVID-19患者内分泌细胞功能的治疗。

Abstract. Recent clinical data has suggested a bidirectional interaction between Coronavirus disease 19 (COVID-19) and diabetes. Individuals with diabetes and severe obesity are more likely to be complications, and have a higher COVID-19 mortality rate symptomatic . Conversely, new-onset diabetes and severe , are at a higher risk for metabolic complications of pre-existing diabetes have been observed in COVID-19 patients. Thus, there is a strong need to understand the pathology and mechanism of pancreatic dysfunction in COVID-19 patients. Here, we demonstrate the detection of SARS-CoV-2 in pancreatic endocrine cells in autopsy samples from COVID-19 patients. Single cell RNA-seq and immunostaining confirmed that multiple types of pancreatic islet cells are susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS- CoV-2 infection, beta cells show a decreased expression of insulin and the increased expression of alpha and acinar cell markers, including glucagon and PRSS1/trypsin1, respectively, suggesting cellular transdifferentiation. Hyperion technology to examine the pathogenesis of autopsy samples of COVID-19 patients. In addition, we will use human islets and a vascularized human pancreatic organoid models to systematically evaluate the role of direct infection and paracrine inflammation signal on human endocrine cells cellular identities, function and survival. In the proposal, we will apply state-of-art Through this study, we would expect to provide a systematic overview of the pathological changes in the pancreas of COVID-19 patients, as well as a detailed mechanism to understand endocrine cell dysfunction, which will pave the road to the development of novel therapy to protect endocrine cell function in COVID-19 patients.