Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-aortic Cluster Architecture.
Understanding Hematopoietic Stem Cell Development through Functional Correlation of Their Proliferative Status with the Intra-aortic Cluster Architecture.
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DOI：
10.1016/j.stemcr.2017.04.003
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发表时间：
2017-06-06
影响因子：
5.9
通讯作者：
Medvinsky A
中科院分区：
文献类型：
--
作者：
Batsivari A;Rybtsov S;Souilhol C;Binagui-Casas A;Hills D;Zhao S;Travers P;Medvinsky A
在发育过程中，造血干细胞（HSC）通过多步成熟和扩增过程出现在性腺-中肾（AGM）区域。虽然成年HSC的增殖与自我更新和分化之间的平衡有关，但对AGM区新生HSC的增殖状态知之甚少。使用能够在体内可视化细胞周期状态的Fucci报告小鼠，我们检测到在HSC前扩增期间增殖增加，然后一旦细胞开始获得确定的HSC状态，就减慢循环，类似于胎肝HSC。我们观察到对应于HSC成熟阶段的主动脉内造血簇的时间特异性变化。簇的增殖结构以有序的解剖学方式维持，其中缓慢循环的细胞在基部，更活跃地增殖的细胞在簇的更顶端部分，这与c-KIT表达水平相关，从而为SCF在HSC成熟中的作用提供解剖学基础。HSC前体的扩增伴随着增殖的增加，HSC成熟的最后步骤伴随着增殖的减速，在HSC发育期间维持主动脉内簇的增殖结构，c-Kit表达水平与HSC前体的增殖状态相关。在这篇文章中，Medvinsky和同事研究了发育中HSC的增殖状态。他们发现，AGM区域中成熟HSC的扩增是由细胞增殖支持的，这可能是由c-Kit/SCF（干细胞因子）信号调节的。他们报道了与HSC成熟相关的主动脉内造血簇的增殖结构在AGM发育阶段得以维持。
During development, hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region through a process of multi-step maturation and expansion. While proliferation of adult HSCs is implicated in the balance between self-renewal and differentiation, very little is known about the proliferation status of nascent HSCs in the AGM region. Using Fucci reporter mice that enable in vivo visualization of cell-cycle status, we detect increased proliferation during pre-HSC expansion followed by a slowing down of cycling once cells start to acquire a definitive HSC state, similar to fetal liver HSCs. We observe time-specific changes in intra-aortic hematopoietic clusters corresponding to HSC maturation stages. The proliferative architecture of the clusters is maintained in an orderly anatomical manner with slowly cycling cells at the base and more actively proliferating cells at the more apical part of the cluster, which correlates with c-KIT expression levels, thus providing an anatomical basis for the role of SCF in HSC maturation. Expansion of HSC precursors is accompanied by increased proliferation Final steps of HSC maturation are accompanied by decelerating proliferation Proliferative architecture of intra-aortic clusters is maintained during HSC development c-Kit expression levels correlate with the proliferative status of HSC precursors In this article, Medvinsky and colleagues studied the proliferative status of developing HSCs. They found that expansion of maturing HSCs in the AGM region is underpinned by cell proliferation, which is likely regulated by c-Kit/SCF (stem cell factor) signaling. They report that the proliferative architecture of intra-aortic hematopoietic clusters which is related to HSC maturation is maintained during the AGM developmental stage.