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

抽象的。 最近的临床数据表明，冠状病毒病19(新冠肺炎)和 糖尿病。 患有糖尿病和严重肥胖的人更有可能 并发症，并有较高的新冠肺炎 死亡率 有症状的 。相反，新发的糖尿病和严重的 ，面临着更高的风险 新冠肺炎患者中观察到了既往糖尿病的代谢并发症。因此，有一个 迫切需要了解新冠肺炎患者胰腺功能障碍的病理和机制。这里, 我们在新冠肺炎尸检样本中的胰腺内分泌细胞中检测到SARS-CoV-2 病人。单细胞rna-seq和免疫组织化学染色证实多种类型的胰岛细胞 容易感染SARS-CoV-2，引发细胞应激反应和趋化因子的诱导。在非典之后- CoV-2感染后，β细胞表现为胰岛素表达降低，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PRSS1/胰蛋白酶1，提示细胞 转分化。 Hyperion技术检测尸检标本的致病机理 新冠肺炎患者的比例。此外，我们将使用人类胰岛和带血管的人类胰腺器官。 系统评价直接感染和旁分泌炎症信号对人体影响的模型 内分泌细胞的细胞特性、功能和生存。 在提案中，我们将应用最先进的技术 通过这项研究，我们希望提供一个 系统概述新冠肺炎患者胰腺的病理变化，以及详细的 了解内分泌细胞功能障碍的机制，将为小说的发展铺平道路 新冠肺炎患者保护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.