Hou Xianliang, Yang Yane, Li Ping, Zeng Zhipeng, Hu Wenlong, Zhe Ruilian, Liu Xinqiong, Tang Donge, Ou Minglin, Dai Yong
Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
The First Affiliated Hospital, Jinan University, Guangzhou, China.
Front Cell Dev Biol. 2021 May 20;9:652408. doi: 10.3389/fcell.2021.652408. eCollection 2021.
The liver is one of vital organs of the human body, and it plays an important role in the metabolism and detoxification. Moreover, fetal liver is one of the hematopoietic places during ontogeny. Understanding how this complex organ develops during embryogenesis will yield insights into how functional liver replacement tissue can be engineered and how liver regeneration can be promoted. Here, we combine the advantages of single-cell RNA sequencing and Spatial Transcriptomics (ST) technology for unbiased analysis of fetal livers over developmental time from 8 post-conception weeks (PCW) and 17 PCW in humans. We systematically identified nine cell types, and defined the developmental pathways of the major cell types. The results showed that human fetal livers experienced blood rapid growth and immigration during the period studied in our experiments, and identified the differentially expressed genes, and metabolic changes in the developmental process of erythroid cells. In addition, we focus on the expression of liver disease related genes, and found that 17 genes published and linked to liver disease mainly expressed in megakaryocyte and endothelial, hardly expressed in any other cell types. Together, our findings provide a comprehensive and clear understanding of the differentiation processes of all main cell types in the human fetal livers, which may provide reference data and information for liver disease treatment and liver regeneration.
肝脏是人体重要器官之一,在新陈代谢和解毒过程中发挥着重要作用。此外,胎儿肝脏是个体发育过程中的造血场所之一。了解这个复杂器官在胚胎发育过程中的发育情况,将有助于深入了解如何构建功能性肝脏替代组织以及如何促进肝脏再生。在这里,我们结合单细胞RNA测序和空间转录组学(ST)技术的优势,对人类从受孕后8周(PCW)到17周PCW发育阶段的胎儿肝脏进行无偏分析。我们系统地鉴定出九种细胞类型,并确定了主要细胞类型的发育途径。结果表明,在我们实验研究的时间段内,人类胎儿肝脏经历了血液的快速生长和迁移,鉴定出差异表达基因以及红细胞发育过程中的代谢变化。此外,我们关注与肝脏疾病相关基因的表达,发现已发表的与肝脏疾病相关的17个基因主要在巨核细胞和内皮细胞中表达,在其他任何细胞类型中几乎不表达。总之,我们的研究结果为人类胎儿肝脏中所有主要细胞类型的分化过程提供了全面而清晰的认识,这可能为肝脏疾病治疗和肝脏再生提供参考数据和信息。