Roundabout 4 is expressed on hematopoietic stem cells and potentially involved in the niche-mediated regulation of the side population phenotype.
Roundabout 4 is expressed on hematopoietic stem cells and potentially involved in the niche-mediated regulation of the side population phenotype.
复制标题
DOI：
10.1634/stemcells.2008-0292
复制
发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Nakajima H
中科院分区：
文献类型：
--
作者：
Shibata F;Goto-Koshino Y;Morikawa Y;Komori T;Ito M;Fukuchi Y;Houchins JP;Tsang M;Li DY;Kitamura T;Nakajima H
Roundabout（Robo）家族蛋白是主要在神经系统中表达的免疫球蛋白型细胞表面受体。该家族的第四个成员Robo 4与其他家族成员不同，因为它在内皮细胞中特异性表达。在这项研究中，我们研究了Robo 4在造血干细胞（HSC）中的表达及其在HSC调控中的可能作用。Robo 4 mRNA在小鼠HSC和未成熟祖细胞组分中特异性表达，但不在谱系阳性细胞或分化的祖细胞中表达。流式细胞术显示Robo 4的高表达与造血细胞的不成熟表型相关。Robo 4 high造血干/祖细胞分别通过集落测定或移植测定显示出更高的克隆形成活性或长期再增殖活性。Robo 4的配体Slit 2在骨髓基质细胞中特异性表达，并且其表达在成骨细胞中响应于骨髓抑制应激而被诱导。有趣的是，HSC中Robo 4或Slit 2的过表达导致它们在c-Kit+Sca-1+谱系-侧群体分数中的驻留减少。这些结果表明，Robo 4在HSC中表达，并且Robo 4/Slit 2信号传导可能在骨髓生态位中的HSC稳态中发挥作用。
Roundabout (Robo) family proteins are immunoglobulin-type cell surface receptors that are expressed predominantly in the nervous system. The fourth member of this family, Robo4, is distinct from the other family members in that it is expressed specifically in endothelial cells. In this study, we examined the expression of Robo4 in hematopoietic stem cells (HSCs) and its possible role in HSC regulation. Robo4 mRNA was specifically expressed in murine HSCs and the immature progenitor cell fraction but not in lineage-positive cells or differentiated progenitors. Moreover, flow cytometry showed a correlation between higher expression of Robo4 and immature phenotypes of hematopoietic cells. Robo4high hematopoietic stem/progenitor cells presented higher clonogenic activity or long-term repopulating activity by colony assays or transplantation assays, respectively. A ligand for Robo4, Slit2, is specifically expressed in bone marrow stromal cells, and its expression was induced in osteoblasts in response to myelosuppressive stress. Interestingly, overexpression of Robo4 or Slit2 in HSCs resulted in their decreased residence in the c-Kit+Sca-1+Lineage−-side population fraction. These results indicate that Robo4 is expressed in HSCs, and Robo4/Slit2 signaling may play a role in HSC homeostasis in the bone marrow niche.
登录
查看更多内容
影响因子：
64.5
作者：
Brose, K;Bland, KS;Kidd, T
通讯作者：
Kidd, T
影响因子：
21.3
作者：
Rhee, J;Mahfooz, NS;VanBerkum, MFA
通讯作者：
VanBerkum, MFA
DOI：
10.1073/pnas.2434383100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Goolsby, J;Marty, MC;Trisler, D
通讯作者：
Trisler, D
影响因子：
4.4
作者：
Huminiecki, L;Gorn, M;Bicknell, R
通讯作者：
Bicknell, R
影响因子：
2.7
作者：
Park, KW;Morrison, CM;Li, DY
通讯作者：
Li, DY