Dr. Li Dak-Sum Research Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong.
Dr. Li Dak-Sum Research Centre, The University of Hong Kong - Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong; Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
J Hepatol. 2020 Dec;73(6):1391-1403. doi: 10.1016/j.jhep.2020.06.012. Epub 2020 Jun 16.
Biliary atresia (BA) is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. In this study, we aimed to investigate the underlying pathogenesis and molecular signatures associated with BA.
We combined organoid and transcriptomic analysis to gain new insights into BA pathobiology using patient samples and a mouse model of BA.
Liver organoids derived from patients with BA and a rhesus rotavirus A-infected mouse model of BA, exhibited aberrant morphology and disturbed apical-basal organization. Transcriptomic analysis of BA organoids revealed a shift from cholangiocyte to hepatocyte transcriptional signatures and altered beta-amyloid-related gene expression. Beta-amyloid accumulation was observed around the bile ducts in BA livers and exposure to beta-amyloid induced the aberrant morphology in control organoids.
The novel observation that beta-amyloid accumulates around bile ducts in the livers of patients with BA has important pathobiological implications, as well as diagnostic potential.
Biliary atresia is a poorly understood and devastating obstructive bile duct disease of newborns. It is often diagnosed late, is incurable and frequently requires liver transplantation. Using human and mouse 'liver mini-organs in the dish', we unexpectedly identified beta-amyloid deposition - the main pathological feature of Alzheimer's disease and cerebral amyloid angiopathy - around bile ducts in livers from patients with biliary atresia. This finding reveals a novel pathogenic mechanism that could have important diagnostic and therapeutic implications.
胆道闭锁（BA）是一种病因不明且具有破坏性的新生儿胆管梗阻性疾病。该病通常诊断较晚，无法治愈，且常需进行肝移植。本研究旨在探究与 BA 相关的潜在发病机制和分子特征。
我们结合类器官和转录组分析，利用患者样本和 BA 的恒河猴轮状病毒 A 感染模型，深入了解 BA 的病理生物学。
源自 BA 患者和 BA 恒河猴轮状病毒 A 感染模型的肝脏类器官表现出异常形态和紊乱的顶底极性组织。BA 类器官的转录组分析显示，胆系细胞向肝细胞转录特征转变，β-淀粉样相关基因表达改变。BA 肝脏中胆管周围可见β-淀粉样物质蓄积，且β-淀粉样物质暴露于对照类器官可诱导其出现异常形态。
BA 患者肝脏胆管周围β-淀粉样物质蓄积的这一新颖观察结果具有重要的病理生物学意义，且具有诊断潜力。
胆道闭锁是一种病因不明且具有破坏性的新生儿胆管梗阻性疾病。该病通常诊断较晚，无法治愈，且常需进行肝移植。利用人类和小鼠“肝脏迷你器官”，我们意外地发现 BA 患者肝脏胆管周围有β-淀粉样物质沉积——阿尔茨海默病和脑淀粉样血管病的主要病理特征。这一发现揭示了一种新的致病机制，可能具有重要的诊断和治疗意义。
