PDF(Pubmed)
Abstract：
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.
摘要：
罕见的多能干细胞通过耗时的过程每秒补充数百万个血细胞，通过越来越多的谱系限制祖细胞的多个阶段。尽管对血液形成系统的损害凸显了从干细胞中更快速补充血液的必要性，建立的造血模型暗示每个血细胞谱系只有一个强制性分化途径。这里,我们在补充所有血细胞谱系的不同干细胞和几乎完全补充血小板的干细胞之间建立了非分级关系，一种对止血至关重要的谱系，在先天和适应性免疫系统中都有重要作用。这些不同的干细胞利用细胞，补充分子独特的巨核细胞限制性祖细胞的分子和功能分离途径：较慢的稳态多能途径和快速通道的紧急激活血小板限制性途径。这些发现提供了在血小板缓慢恢复仍然是主要临床挑战的环境中增强血小板补充的框架。
