Blaser Bradley W, Moore Jessica L, Hagedorn Elliott J, Li Brian, Riquelme Raquel, Lichtig Asher, Yang Song, Zhou Yi, Tamplin Owen J, Binder Vera, Zon Leonard I
Stem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Medical School, Harvard Stem Cell Institute, Stem Cell and Regenerative Biology Department, Harvard University, Boston, MA 02138.
Department of Pharmacology, The University of Illinois College of Medicine, Chicago, IL 60612.
J Exp Med. 2017 Apr 3;214(4):1011-1027. doi: 10.1084/jem.20161616. Epub 2017 Mar 28.
The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Recent advances marking fluorescent HSPCs have allowed exquisite visualization of HSPCs in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Here, we show that the chemokine and its receptor, , are expressed by zebrafish endothelial cells, and we identify signaling as a positive regulator of HSPC colonization. Single-cell tracking experiments demonstrated that this is a result of increases in HSPC-endothelial cell "cuddling," HSPC residency time within the CHT, and HSPC mitotic rate. Enhanced signaling was associated with an increase in the volume of the CHT and induction of expression. Finally, using parabiotic zebrafish, we show that acts HSPC nonautonomously to improve the efficiency of donor HSPC engraftment. This work identifies a mechanism by which the hematopoietic niche remodels to promote HSPC engraftment and suggests that signaling is a potential therapeutic target in patients undergoing hematopoietic stem cell transplantation.
微环境是造血干细胞和祖细胞（HSPC）生物学的重要调节因子。近期对荧光HSPC进行标记的进展使得在发育中的斑马鱼的尾造血组织（CHT）中能够精确可视化HSPC。在此，我们表明趋化因子及其受体由斑马鱼内皮细胞表达，并且我们确定信号传导是HSPC定植的正向调节因子。单细胞追踪实验表明，这是HSPC与内皮细胞“依偎”增加、HSPC在CHT内的驻留时间以及HSPC有丝分裂率增加的结果。增强的信号传导与CHT体积增加和表达的诱导相关。最后，使用联体斑马鱼，我们表明以非自主方式作用于HSPC以提高供体HSPC植入的效率。这项工作确定了造血微环境重塑以促进HSPC植入的机制，并表明信号传导是接受造血干细胞移植患者的潜在治疗靶点。
