Mooney Ciaran James, Cunningham Alan, Tsapogas Panagiotis, Toellner Kai-Michael, Brown Geoffrey
Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Basel 4058, Switzerland.
Int J Mol Sci. 2017 May 12;18(5):1037. doi: 10.3390/ijms18051037.
The fms-like tyrosine kinase 3 (Flt3) is a cell surface receptor that is expressed by various hematopoietic progenitor cells (HPC) and Flt3-activating mutations are commonly present in acute myeloid and lymphoid leukemias. These findings underscore the importance of Flt3 to steady-state and malignant hematopoiesis. In this study, the expression of Flt3 protein and mRNA by single cells within the hematopoietic stem cell (HSC) and HPC bone marrow compartments of C57/BL6 mice was investigated using flow cytometry and the quantitative reverse transcription polymerase chain reaction. Flt3 was heterogeneously expressed by almost all of the populations studied, including long-term reconstituting HSC and short-term reconstituting HSC. The erythropoietin receptor (EpoR) and macrophage colony-stimulating factor receptor (M-CSFR) were also found to be heterogeneously expressed within the multipotent cell compartments. Co-expression of the mRNAs encoding Flt3 and EpoR rarely occurred within these compartments. Expression of both Flt3 and M-CSFR protein at the surface of single cells was more commonly observed. These results emphasize the heterogeneous nature of HSC and HPC and the new sub-populations identified are important to understanding the origin and heterogeneity of the acute myeloid leukemias.
Fms样酪氨酸激酶3（Flt3）是一种细胞表面受体，由多种造血祖细胞（HPC）表达，Flt3激活突变常见于急性髓系和淋巴细胞白血病中。这些发现强调了Flt3对稳态和恶性造血的重要性。在本研究中，使用流式细胞术和定量逆转录聚合酶链反应，研究了C57/BL6小鼠造血干细胞（HSC）和HPC骨髓区室中单个细胞Flt3蛋白和mRNA的表达。几乎所有研究的群体，包括长期重建HSC和短期重建HSC，Flt3均呈异质性表达。促红细胞生成素受体（EpoR）和巨噬细胞集落刺激因子受体（M-CSFR）在多能细胞区室中也呈异质性表达。在这些区室中，编码Flt3和EpoR的mRNA很少共表达。更常见的是在单个细胞表面同时观察到Flt3和M-CSFR蛋白的表达。这些结果强调了HSC和HPC的异质性，新鉴定的亚群对于理解急性髓系白血病的起源和异质性很重要。
