小柯机器人

英国伦敦国王学院Francesca M. Spagnoli小组近日取得一项新成果。经过不懈努力，他们的最新研究通过定量谱系分析揭示了肝-胰-胆祖细胞的生态位。该研究成果在线发表在2021年8月25日出版的《自然》上。

研究人员利用计算建模与遗传谱系追踪相结合的方法，准确重建了肝-胰-胆谱系树。研究表明，多能祖细胞亚群持续存在于胰胆器官雏形中，不仅为胰腺和胆囊提供细胞，还为肝脏生成提供了细胞。

此外，使用单细胞RNA测序和功能实验，研究人员发现了一个专门的生态位，在细胞分化过程中长时间维持了该亚群的多能状态。这些发现共同表明肝-胰-胆管发育的持续可塑性，这也可能解释了肝脏快速扩张时胰胆管生长减弱的原因。 

据了解，单细胞研究揭示了干细胞和祖细胞区室中明显的细胞异质性，这表明连续分化轨迹与细胞在不同谱系定型状态下的混合以及器官发生过程中强大的细胞可塑性。肝-胰-胆器官系统来源于内胚层中一个小的区室，它产生各种不同的成体组织，包括肝脏、胰腺、胆囊和肝外胆管。小鼠胚胎中各种发育信号的实验操作揭示了胚胎中该区室强大的细胞可塑性。这反映在人类遗传综合征以及以肝脏、胰腺和胆囊中多器官表型为特征的先天畸形上。然而，导致内胚层祖细胞区室分化成肝、胆和胰腺结构的精确谱系层次和分化顺序尚未确定。

附：英文原文

Title: Quantitative lineage analysis identifies a hepato-pancreato-biliary progenitor niche

Author: Willnow, David, Benary, Uwe, Margineanu, Anca, Vignola, Maria Lillina, Konrath, Fabian, Pongrac, Igor M., Karimaddini, Zahra, Vigilante, Alessandra, Wolf, Jana, Spagnoli, Francesca M.

Issue&Volume: 2021-08-25

Abstract: Studies based on single cells have revealed vast cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degrees of plasticity during organogenesis1,2,3,4,5. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including the liver, pancreas, gall bladder and extra-hepatic bile ducts6,7. Experimental manipulation of various developmental signals in the mouse embryo has underscored important cellular plasticity in this embryonic territory6. This is reflected in the existence of human genetic syndromes as well as congenital malformations featuring multi-organ phenotypes in liver, pancreas and gall bladder6. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary and pancreatic structures have not yet been established. Here we combine computational modelling approaches with genetic lineage tracing to accurately reconstruct the hepato-pancreato-biliary lineage tree. We show that a multipotent progenitor subpopulation persists in the pancreato-biliary organ rudiment, contributing cells not only to the pancreas and gall bladder but also to the liver. Moreover, using single-cell RNA sequencing and functional experiments we define a specialized niche that supports this subpopulation in a multipotent state for an extended time during development. Together these findings indicate sustained plasticity underlying hepato-pancreato-biliary development that might also explain the rapid expansion of the liver while attenuating pancreato-biliary growth.

DOI: 10.1038/s41586-021-03844-1

Source: https://www.nature.com/articles/s41586-021-03844-1

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html