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A novel family of slitrk genes is expressed on hematopoietic stem cells and leukemias

Leukemia volume 21, pages 824–827 (2007)Cite this article

To assess expression patterns of slitrks by primary cells, we studied the expression of slitrk genes on human mononuclear cells (MNC) isolated from peripheral blood, human umbilical vein endothelial cells (HUVEC), human fetal bone stroma (BS), human foreskin fibroblast (HFF) and human umbilical vein stroma cells (HUVSC), and human Miz-hES5 embryonic stem cells by reverse transcriptase-polymerase chain reaction (RT-PCR). All six members of the slitrk family were expressed by human embryonic stem cells (ESC) (Figure 1c). To exclude the possibility of contamination by mouse embryonic fibroblast (MEF) feeder cells, we demonstrated that human slitrk members were not expressed by MEF using the same set of primers. Human fetal BS showed a pattern similar to that of ESC, as did HUVSC, with all six members of slitrks being expressed on these cells. However, adult HFF showed a different and more specific pattern, expressing only slitrk1 and slitrk6 (Figure 1a). This suggests that embryonic and fetal tissues maintain the expression of slitrks during development, in contrast to terminally differentiated cells.

The initial finding of slitrks being expressed on CD34+ leukemic cells prompted us to invesitgate the expression of slitrks on hematopoietic stem and progenitor cells. Hematopoietic CD34+CD38− as well as CD34+ stem and progenitor cells were sorted from human bone marrow (MoFlo High-Performance Cell Sorter, Dako Cytomation, Glostrup, Denmark) and isolated from cord blood and mobilized peripheral blood of healthy donors, respectively (magnetic cell sorting; MACS Miltenyi Biotec Inc., Auburn, CA, USA). qPCR analysis revealed that highly purified population of human CD34+CD38− hematopoietic stem and progenitor cells isolated from bone marrow express slitrk4 and slitrk5, but not other members of the slitrk family. The CD34+CD38+ fraction also expressed slitrk4 and slitrk5, whereas the cells of the CD34− fraction expressed both genes at a very low level (Figure 2b). Human CD34+ hematopoietic progenitor cells isolated from umbilical cord blood also expressed both slitrk4 and slitrk5, whereas the CD34− population expressed significantly lower levels of slitrk4 and slitrk5 (Figure 2b). This pattern is reproduced in the CD34+ and CD34− populations purified from mobilized peripheral blood of healthy donors treated with granulocyte-colony stimulating factor (G-CSF) (Figure 2b).

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Acknowledgements

Till Milde is supported by a grant from the Mildred-Scheel-Stiftung, Deutsche Krebshilfe, Bonn, Germany. Shahin Rafii is supported by the Howard Hughes Medical Institute, the NIH (grants R01 HL075234, R01 HL59312, R01 HL67839, R01 HL61849 and R21 HL083222), The American Cancer Society, and The Leukemia and Lymphoma Society.

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  1. Department of Genetic Medicine, The Howard Hughes Medical Institute, Weill Medical College of Cornell University, New York, NY, USA

    T Milde, S V Shmelkov, G Zlotchenko, I Petit & S Rafii

  2. The Department of Pediatrics, Weill Medical College of Cornell University, New York, NY, USA

    K K Jensen

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Correspondence to S Rafii.

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Milde, T., Shmelkov, S., Jensen, K. et al. A novel family of slitrk genes is expressed on hematopoietic stem cells and leukemias. Leukemia 21, 824–827 (2007). https://doi.org/10.1038/sj.leu.2404525

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