Loss of EfnB1 in the osteogenic lineage compromises their capacity to support hematopoietic stem/progenitor cell maintenance

被引：13
作者：
Arthur, Agnieszka [1 ,2 ]
Nguyen, Thao M. [1 ,2 ]
Paton, Sharon [1 ,2 ]
Zannettino, Andrew C. W. [2 ,3 ]
Gronthos, Stan [1 ,2 ]
机构：
[1] Univ Adelaide, Mesenchymal Stem Cell Lab, Adelaide Med Sch, Fac Hlth & Med Sci, North Terrace, Adelaide, SA 5005, Australia
[2] South Australian Hlth & Med Res Inst, Canc Theme, Adelaide, SA, Australia
[3] Univ Adelaide, Adelaide Med Sch, Fac Hlth & Med Sci, Myeloma Res Lab, Adelaide, SA, Australia
来源：
EXPERIMENTAL HEMATOLOGY | 2019年 / 69卷
基金：
英国医学研究理事会;
关键词：
STEM-CELLS; IN-VIVO; EPH RECEPTORS; ENDOCHONDRAL OSSIFICATION; BONE; EPHRIN-B1; DIFFERENTIATION; PROGENITORS; MIGRATION; NICHE;
D O I：
10.1016/j.exphem.2018.10.004
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
The bone marrow stromal microenvironment contributes to the maintenance and function of hematopoietic stem/progenitor cells (HSPCs). The Eph receptor tyrosine kinase family members have been implicated in bone homeostasis and stromal support of HSPCs. The present study examined the influence of EfnB1-expressing osteogenic lineage on HSPC function. Mice with conditional deletion of EfnB1 in the osteogenic lineage (EfnB1(OB)(-/-)), driven by the Osterix promoter, exhibited a reduced prevalence of osteogenic progenitors and osteoblasts, correlating to lower numbers of HSPCs compared with Osx:Cre mice. Long-term culture-initiating cell (LTC-IC) assays confirmed that the loss of EfnB1 within bone cells hindered HSPC function, with a significant reduction in colony formation in EfnB1(OB)(-/-) mice compared with Osx:Cre mice. Human studies confirmed that activation of EPHB2 on CD34(+) HSPCs via EFNB1-Fc stimulation enhanced myeloid/erythroid colony formation, whereas functional blocking of either EPHB1 or EPHB2 inhibited the maintenance of LTC-ICs. Moreover, EFNB1 reverse signaling in human and mouse stromal cells was found to be required for the activation of the HSPC-promoting factor CXCL12. Collectively, the results of this study confirm that EfnB1 contributes to the stromal support of HSPC function and maintenance and may be an important factor in regulating the HSPC niche. (C) 2018 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
引用
收藏
页码：43 / 53
页数：11
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