论文
论文标题：Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality
作者：Samuel J. Wattrus, Mackenzie L. Smith , Cecilia Pessoa Rodrigues, Elliott J. Hagedorn, Ji Wook Kim , et al.
期刊：Science
发表时间：2022/09/22
数字识别码：10.1126/science.abo4837
摘要：Tissue-specific stem cells persist for a lifetime and can differentiate to maintain homeostasis or transform to initiate cancer. Despite their importance, there are no described quality assurance mechanisms for newly formed stem cells. We observed intimate and specific interactions between macrophages and nascent blood stem cells in zebrafish embryos. Macrophage interactions frequently led to either removal of cytoplasmic material and stem cell division or complete engulfment and stem cell death. Stressed stem cells were marked by surface Calreticulin, which stimulated macrophage interactions. Using cellular barcoding, we found that Calreticulin knock-down or embryonic macrophage depletion reduced the number of stem cell clones that established adult hematopoiesis. Our work supports a model in which embryonic macrophages determine hematopoietic clonality by monitoring stem cell quality.
所属学科：
细胞生物学
撰文丨十一月
在胚胎形成过程中干细胞的数量确保体内细胞谱系的平衡，这对于机体的正常发育非常关键。这些干细胞既然对于正常组织功能这么重要，那么一定需要一些质量保证机制确保干细胞的质量。但目前位置，造血干细胞和祖细胞的质量控制体系还尚不可知。为此，美国哈佛大学Leonard I. Zon研究组在Science发文题为Quality assurance of hematopoietic stem cells by macrophages determines stem cell clonality，发现造血干细胞通过与巨噬细胞相互作用，确保造血干细胞质量从而调节成年时期造血干细胞克隆的数量。
为了研究干细胞质量控制的具体机制，作者们将目光集中在了斑马鱼胚胎的血液发育。斑马鱼造血干细胞和祖细胞（Hematopoietic stem and progenitor cells，HSPCs）从背主动脉腹壁出现进入血液循环，并停留在尾侧造血组织的血管丛（Caudal hematopoietic tissue，CHT）。造血干细胞和祖细胞在CHT中迅速扩张，然后迁移到肾骨髓中。在成体造血细胞龛中，造血干细胞和祖细胞与多种类型的细胞存在相互作用，其中包括血管内皮细胞、间充质细胞以及巨噬细胞。背主动脉腹壁产生的20-30个造血干细胞克隆最终形成成体血液系统【3】。但是来自背主动脉腹壁的新生造血干细胞在建立起成体造血系统之前是否经过质量保证还不得而知。
