Laboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London NW1 1AT, UK.
Bioinformatics core, The Francis Crick Institute, London NW1 1AT, UK.
Sci Adv. 2023 Oct 6;9(40):eadf6911. doi: 10.1126/sciadv.adf6911. Epub 2023 Oct 4.
Stem cell (SC) differentiation and maintenance of resultant progeny underlie cell turnover in many organs, but it is difficult to pinpoint the contribution of either process. In the pituitary, a central regulator of endocrine axes, adult SCs undergo activation after target organ ablation, providing a well-characterized paradigm to study an adaptative response in a multi-organ system. Here, we used single-cell technologies to characterize SC heterogeneity and mobilization together with lineage tracing. We show that SC differentiation occurs more frequently than thought previously. In adaptative conditions, differentiation increases and is more diverse than demonstrated by the lineage tracing experiments. Detailed examination of SC progeny suggests that maintenance of selected nascent cells underlies SC output, highlighting a trophic role for the microenvironment. Analyses of cell trajectories further predict pathways and potential regulators. Our model provides a valuable system to study the influence of evolving states on the mechanisms of SC mobilization.
干细胞 (SC) 的分化和产生的后代的维持是许多器官细胞更新的基础，但很难确定这两个过程中的任何一个的贡献。在作为内分泌轴中枢调节者的垂体中，成年干细胞在靶器官消融后会被激活，为研究多器官系统中的适应性反应提供了一个特征明确的范例。在这里，我们使用单细胞技术来描述干细胞的异质性和动员以及谱系追踪。我们表明，干细胞的分化比以前认为的更为频繁。在适应条件下，分化增加，并且比谱系追踪实验显示的更加多样化。对干细胞后代的详细检查表明，微环境对特定新生细胞的维持是干细胞输出的基础，突出了其营养作用。细胞轨迹的分析进一步预测了途径和潜在的调节剂。我们的模型提供了一个有价值的系统，可以研究不断变化的状态对干细胞动员机制的影响。
