Haematopoietic Stem Cell Biology Laboratory, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Nat Immunol. 2024 Jun;25(6):1007-1019. doi: 10.1038/s41590-024-01845-6. Epub 2024 May 30.
Rare multipotent stem cells replenish millions of blood cells per second through a time-consuming process, passing through multiple stages of increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight the need for more rapid blood replenishment from stem cells, established models of hematopoiesis implicate only one mandatory differentiation pathway for each blood cell lineage. Here, we establish a nonhierarchical relationship between distinct stem cells that replenish all blood cell lineages and stem cells that replenish almost exclusively platelets, a lineage essential for hemostasis and with important roles in both the innate and adaptive immune systems. These distinct stem cells use cellularly, molecularly and functionally separate pathways for the replenishment of molecularly distinct megakaryocyte-restricted progenitors: a slower steady-state multipotent pathway and a fast-track emergency-activated platelet-restricted pathway. These findings provide a framework for enhancing platelet replenishment in settings in which slow recovery of platelets remains a major clinical challenge.
稀有多能干细胞通过一个耗时的过程每秒补充数百万个血细胞，经历多个阶段，逐渐成为谱系受限的祖细胞。虽然血液生成系统受到损伤突出表明需要更快地从干细胞中补充血液，但已建立的造血模型仅暗示每个血细胞谱系都需要一条强制性分化途径。在这里，我们建立了一个在补充所有血细胞谱系的不同干细胞和几乎仅补充血小板的干细胞之间的非层次关系，血小板是止血所必需的谱系，在先天和适应性免疫系统中都有重要作用。这些不同的干细胞使用细胞上、分子上和功能上独立的途径来补充分子上不同的巨核细胞限制祖细胞：一个较慢的稳态多能途径和一个快速通道应急激活的血小板限制途径。这些发现为增强血小板补充提供了一个框架，在血小板恢复缓慢仍然是一个主要临床挑战的情况下，这是非常有意义的。
