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.

罕见的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，并经历谱系日益受限的祖细胞的多个阶段。尽管对造血系统的损害凸显了干细胞更快速补充血液的需要，但已建立的造血模型表明每种血细胞谱系仅存在一种强制分化途径。在这里，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一种非等级关系，血小板是止血所必需的谱系，并且在先天性和适应性免疫系统中发挥着重要作用。这些独特的干细胞使用细胞、分子和功能上独立的途径来补充分子上不同的巨核细胞限制性祖细胞：较慢的稳态多能途径和快速紧急激活的血小板限制性途径。这些发现为在血小板恢复缓慢仍然是主要临床挑战的环境中增强血小板补充提供了一个框架。