A CTX family cell adhesion molecule, JAM4, is expressed in stem cell and progenitor cell populations of both male germ cell and hematopoietic cell lineages
A CTX family cell adhesion molecule, JAM4, is expressed in stem cell and progenitor cell populations of both male germ cell and hematopoietic cell lineages
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DOI：
10.1128/mcb.01502-06
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发表时间：
2006-11-01
影响因子：
5.3
通讯作者：
Ohbo, Kazuyuki
中科院分区：
文献类型：
--
作者：
Nagamatsu, Go;Ohmura, Masako;Ohbo, Kazuyuki
干细胞通过与称为“小生境”的微环境相互作用而维持在未分化状态，所述微环境由各种分泌蛋白和膜蛋白组成。我们的目标是鉴定参与干细胞-干细胞和/或干细胞-支持细胞相互作用的小生境分子。在这里，我们分离的基因编码分泌和膜蛋白纯化的雄性生殖干细胞使用信号序列陷阱的方法。在所鉴定的基因中，我们专注于连接粘附分子4（JAM 4），一种免疫球蛋白型细胞粘附分子。JAM 4蛋白实际上定位于雄性生殖细胞的质膜。随着细胞在生殖细胞和造血细胞谱系中的分化，JAM 4表达下调。为了分析体内功能，我们产生了JAM 4缺陷小鼠。来自纯合子无效的睾丸的组织学分析没有显示出明显的异常，肝和肾组织也没有，这两者都强烈表达JAM 4。骨髓中造血干细胞的数量在野生型和突变型小鼠之间是无法区分的，雄性生殖细胞的发育也是如此。这些结果表明，JAM 4在干细胞和祖细胞中表达，但在雄性生殖细胞和造血谱系中，其他细胞粘附分子可能替代JAM 4缺陷小鼠中的JAM 4功能。
Stem cells are maintained in an undifferentiated state by interacting with a microenvironment known as the "niche," which is comprised of various secreted and membrane proteins. Our goal was to identify niche molecules participating in stem cell-stem cell and/or stem cell-supporting cell interactions. Here, we isolated genes encoding secreted and membrane proteins from purified male germ stem cells using a signal sequence trap approach. Among the genes identified, we focused on the junctional adhesion molecule 4 (JAM4), an immunoglobulin type cell adhesion molecule. JAM4 protein was actually localized to the plasma membrane in male germ cells. JAM4 expression was downregulated as cells differentiated in both germ cell and hematopoietic cell lineages. To analyze function in vivo, we generated JAM4-deficient mice. Histological analysis of testes from homozygous nulls did not show obvious abnormalities, nor did liver and kidney tissues, both of which strongly express JAM4. The numbers of hematopoietic stem cells in bone marrow were indistinguishable between wild-type and mutant mice, as was male germ cell development. These results suggest that JAM4 is expressed in stem cells and progenitor cells but that other cell adhesion molecules may substitute for JAM4 function in JAM4-deficient mice both in male germ cell and hematopoietic lineages.