英国牛津大学Sten Eirik W. Jacobsen研究小组报道了，由非等级相关的造血干细胞启动的血小板分化途径。2024年5月30日，国际知名学术期刊《自然—免疫学》发表了这一成果。

该团队在补充所有血细胞谱系的不同干细胞和几乎只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，在先天和适应性免疫系统中都起着重要作用。这些不同的干细胞在细胞、分子和功能上都有不同的途径，来补充分子上不同的巨核细胞限制性祖细胞——一个较慢的稳态多能途径和一个快速的紧急激活血小板限制性途径。

这些发现为在血小板恢复缓慢仍然是主要临床挑战的情况下，加强血小板补充提供了一个框架。

据了解，罕见的多能干细胞通过一个耗时的过程，每秒补充数以百万计的血细胞，经过越来越多的谱系限制祖细胞的多个阶段。尽管对造血系统的损害强调了干细胞需要更快速的血液补充，但已建立的造血模型表明，每种血细胞谱系只有一条强制性分化途径。

附：英文原文

Title: Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells

Author: Carrelha, Joana, Mazzi, Stefania, Winroth, Axel, Hagemann-Jensen, Michael, Ziegenhain, Christoph, Hgstrand, Kari, Seki, Masafumi, Brennan, Margs S., Lehander, Madeleine, Wu, Bishan, Meng, Yiran, Markljung, Ellen, Norfo, Ruggiero, Ishida, Hisashi, Belander Strlin, Karin, Grasso, Francesca, Simoglou Karali, Christina, Aliouat, Affaf, Hillen, Amy, Chari, Edwin, Siletti, Kimberly, Thongjuea, Supat, Mead, Adam J., Linnarsson, Sten, Nerlov, Claus, Sandberg, Rickard, Yoshizato, Tetsuichi, Woll, Petter S., Jacobsen, Sten Eirik W.

Issue&Volume: 2024-05-30

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.

DOI: 10.1038/s41590-024-01845-6

Source: https://www.nature.com/articles/s41590-024-01845-6