Walker L, Carlson A, Tan-Pertel H T, Weinmaster G, Gasson J
UCLA Molecular Biology Institute, Los Angeles, CA 90095-1781, USA.
Stem Cells. 2001;19(6):543-52. doi: 10.1634/stemcells.19-6-543.
Members of the Notch family of transmembrane receptors are found on primitive hematopoietic precursors, and Notch ligand expression has been demonstrated on the surface of stromal cells, suggesting a role for Notch signaling in mammalian blood cell development. The current report examines the expression of Notch receptors and their ligands in murine hematopoietic tissues to determine: A) which blood cell lineages in the adult are influenced by Notch activity, and B) whether fetal hematopoiesis in the embryo involves the Notch pathway. In the adult mouse, a combination of flow cytometry, immunohistochemistry and Northern analysis was used to examine Notch receptor or ligand expression in bone marrow and spleen. In the embryo, Northern analysis and in situ hybridization were used to characterize Notch receptor and ligand expression in fetal liver on embryonic day 12 (E12) through E17, an active period encompassing both erythropoiesis and granulopoeisis. Flow cytometry demonstrated the presence of Notch1 and Notch2 receptors on bone marrow-derived myeloid cells but not on erythroid cells positive for the marker, Ter-119. In situ hybridization of E12 through E17 fetal liver demonstrated widespread expression of Jagged1 and Delta1 in a pattern similar to but less abundant than that of the erythropoietin receptor. Taken together with earlier functional results, the current expression data suggest a role for Notch activity in establishing definitive hematopoiesis in fetal liver, as well as a selective use of Notch signaling in adult erythropoiesis and granulopoiesis. Notch receptors in the adult are most likely utilized by early erythroid precursors and intermediate-stage granulocytes, but not by terminally differentiating cells of either subset.
跨膜受体Notch家族的成员存在于原始造血前体细胞上,并且已经证实在基质细胞表面有Notch配体表达,这表明Notch信号传导在哺乳动物血细胞发育中发挥作用。本报告研究了Notch受体及其配体在小鼠造血组织中的表达,以确定:A)成体中哪些血细胞谱系受Notch活性影响,以及B)胚胎中的胎儿造血是否涉及Notch途径。在成年小鼠中,采用流式细胞术、免疫组织化学和Northern分析相结合的方法,检测骨髓和脾脏中Notch受体或配体的表达。在胚胎中,采用Northern分析和原位杂交技术,对胚胎第12天(E12)至E17天胎儿肝脏中Notch受体和配体的表达进行了表征,这一活跃期涵盖了红细胞生成和粒细胞生成过程。流式细胞术显示,骨髓来源的髓样细胞上存在Notch1和Notch2受体,但标记为Ter-119的红细胞上不存在。对E12至E17天胎儿肝脏进行原位杂交显示,Jagged1和Delta1广泛表达,其模式与促红细胞生成素受体相似,但丰度较低。结合早期的功能研究结果,目前的表达数据表明,Notch活性在胎儿肝脏中建立确定性造血过程中发挥作用,并且在成体红细胞生成和粒细胞生成中选择性地使用Notch信号传导。成体中的Notch受体最有可能被早期红细胞前体细胞和中期粒细胞利用,但不被这两个亚群的终末分化细胞利用。