英国剑桥大学Ludovic Vallier课题组绘制人类肝脏发育的单细胞图谱，揭示了指导肝细胞命运的途径。2022年9月15日出版的《自然—细胞生物学》杂志发表了这项成果。

他们通过描述以单细胞分辨率构成人类肝脏的不同细胞类型的发育轨迹来解决阻碍肝脏治疗的问题。这些转录组学分析表明，连续的细胞间相互作用指导肝细胞的功能成熟，非实质细胞在器官发生过程中发挥重要作用。他们利用这些信息推导出双能肝母细胞类器官，然后利用该模型系统验证信号通路在肝细胞和胆管细胞规格中的重要性。对肝脏成熟的进一步了解还能够识别特定阶段的转录因子，以改善由人类多能干细胞产生的肝细胞样细胞的功能。因此，他们的研究建立了一个平台来研究指导人类肝脏发育的基本机制，并产生用于临床应用的细胞类型。

据悉，由于影响其重要功能的疾病种类繁多，肝脏已被广泛研究。然而，由于缺乏有关人类肝脏发育的知识，治疗进展受到了阻碍。

附：英文原文

Title: Single-cell atlas of human liver development reveals pathways directing hepatic cell fates

Author: Wesley, Brandon T., Ross, Alexander D. B., Muraro, Daniele, Miao, Zhichao, Saxton, Sarah, Tomaz, Rute A., Morell, Carola M., Ridley, Katherine, Zacharis, Ekaterini D., Petrus-Reurer, Sandra, Kraiczy, Judith, Mahbubani, Krishnaa T., Brown, Stephanie, Garcia-Bernardo, Jose, Alsinet, Clara, Gaffney, Daniel, Horsfall, Dave, Tysoe, Olivia C., Botting, Rachel A., Stephenson, Emily, Popescu, Dorin-Mirel, MacParland, Sonya, Bader, Gary, McGilvray, Ian D., Ortmann, Daniel, Sampaziotis, Fotios, Saeb-Parsy, Kourosh, Haniffa, Muzlifah, Stevens, Kelly R., Zilbauer, Matthias, Teichmann, Sarah A., Vallier, Ludovic

Issue&Volume: 2022-09-15

Abstract: The liver has been studied extensively due to the broad number of diseases affecting its vital functions. However, therapeutic advances have been hampered by the lack of knowledge concerning human hepatic development. Here, we addressed this limitation by describing the developmental trajectories of different cell types that make up the human liver at single-cell resolution. These transcriptomic analyses revealed that sequential cell-to-cell interactions direct functional maturation of hepatocytes, with non-parenchymal cells playing essential roles during organogenesis. We utilized this information to derive bipotential hepatoblast organoids and then exploited this model system to validate the importance of signalling pathways in hepatocyte and cholangiocyte specification. Further insights into hepatic maturation also enabled the identification of stage-specific transcription factors to improve the functionality of hepatocyte-like cells generated from human pluripotent stem cells. Thus, our study establishes a platform to investigate the basic mechanisms directing human liver development and to produce cell types for clinical applications.

DOI: 10.1038/s41556-022-00989-7

Source: https://www.nature.com/articles/s41556-022-00989-7