Sivakumar Aravind, Frank David B
Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Penn-CHOP Lung Biology Institute, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Curr Stem Cell Rep. 2019 Dec;5(4):133-144. doi: 10.1007/s40778-019-00166-x. Epub 2019 Nov 18.
Throughout the lifespan, lung injury impedes the primary critical function essential for life-respiration. To repair quickly and efficiently is critical and is orchestrated by a diverse repertoire of progenitor cells and their niche. This review incorporates knowledge gained from early studies in lung epithelial morphogenesis and cell fate and explores its relevance to more recent findings of lung progenitor and stem cells in development and regeneration.
Cell fate in the lung is organized into an early specification phase and progressive differentiation phase in lung development. The advent of single cell analysis combined with lineage analysis and projections is uncovering new functional cell types in the lung providing a topographical atlas for progenitor cell lineage commitment during development, homeostasis, and regeneration.
Lineage commitment of lung progenitor cells is spatiotemporally regulated during development. Single cell sequencing technologies have significantly advanced our understanding of the similarities and differences between developmental and regenerative cell fate trajectories. Subsequent unraveling of the molecular mechanisms underlying these cell fate decisions will be essential to manipulating progenitor cells for regeneration.
在整个生命周期中,肺损伤会阻碍维持生命呼吸所必需的主要关键功能。快速有效地修复至关重要,这是由多种祖细胞及其生态位精心协调完成的。本综述整合了早期肺上皮形态发生和细胞命运研究中获得的知识,并探讨其与肺祖细胞和干细胞在发育和再生方面最新研究结果的相关性。
在肺发育过程中,肺内的细胞命运被组织成早期特化阶段和渐进分化阶段。单细胞分析与谱系分析及预测相结合的方法正在揭示肺内新的功能细胞类型,为发育、稳态和再生过程中祖细胞谱系的定向分化提供了一个拓扑图谱。
肺祖细胞的谱系定向分化在发育过程中受到时空调节。单细胞测序技术极大地推进了我们对发育和再生细胞命运轨迹异同的理解。随后阐明这些细胞命运决定背后的分子机制对于操纵祖细胞进行再生至关重要。