Murdoch Children's Research Institute, Parkville, Australia.
School of Biosciences, University of Melbourne, Melbourne, Australia.
Elife. 2019 Jan 24;8:e41156. doi: 10.7554/eLife.41156.
Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here, we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express , an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling of returning cells reveals that nephron progenitors can traverse the transcriptional hierarchy between self-renewal and commitment in either direction. This plasticity may enable robust regulation of nephrogenesis as niches remodel and grow during organogenesis.
祖细胞的自我更新和分化通常受到组织微环境中空间限制信号的调控。在这里,我们研究了祖细胞迁移如何影响小鼠肾发生龛内局部诱导的祖细胞向特定细胞分化。我们发现了一小部分表达早期肾单位分化标志物的细胞,但它们会迁移回祖细胞群体中,并随着时间的推移逐渐积累。对返回细胞的单细胞 RNA 测序和计算模型分析表明,肾祖细胞可以在自我更新和分化之间的转录层次结构中双向穿梭。这种可塑性可能使肾发生在器官发生过程中龛重塑和生长时能够得到稳健的调控。