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Expression of the lymphoid enhancer factor 1 is required for normal hematopoietic stem and progenitor cell function

Leukemia volume 28, pages 227–230 (2014)Cite this article

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To exclude the possibility that Lef-1 knockdown compromises HSC function via impairing homing of transplanted cells, shRNA-transduced BM cells were injected intrafemorally into recipient mice. The level of engraftment was significantly reduced in BM cells transduced with shRNA7 compared to the scrambled control comparable to the results after intravenous injection (shscr 2.43±0.94 (s.e.m.) versus shRNA7 with 0.58±0.21; n=8-9; P<0.01, Figure1c), pointing to a cell intrinsic effect of Lef-1 downregulation at the level of HSCs. Of note, there was no difference in the lineage differentiation of cells infected with the shRNA7 versus the scrambled construct in vivo.

Taken together, these data demonstrate that Lef-1 is an important factor for HSC and progenitor function and that its stem cell regulatory role depends on its DNA binding ability. These data are in line but substantially extend data in the human system showing that shRNA-mediated suppression of LEF-1 in human granulocyte-colony-stimulating factor-primed peripheral CD34+ cells impair proliferation and survival in vitro.2 Deciphering why normal HSCs depend on Lef-1 expression and to which extent this is Wnt independent will greatly facilitate our understanding of the aberrant function of LEF-1 in human leukemias.

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Acknowledgements

We thank Bernd Baumann for his advice in the electrophoretic mobility shift assay and Stefanie Dannenmann and Florian Blum (Core Facility ‘FACS’, Medical Faculty Ulm) for their help in fluorescence activated cell sorting. This work was supported by the DFG (SFB 1074 project A4). KE is the member of the International Graduate School in Molecular Medicine Ulm (IGradU), funded by the Excellence Initiative of the German Federal and State Governments.

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  1. Institute of Experimental Cancer Research, Comprehensive Cancer Center, Ulm, Germany

    K E Edmaier, K Stahnke, N Vegi, M Mulaw, S Ihme & C Buske

  2. Institute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Aging, Ulm, Germany

    A Scheffold & K L Rudolph

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Correspondence to C Buske.

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Edmaier, K., Stahnke, K., Vegi, N. et al. Expression of the lymphoid enhancer factor 1 is required for normal hematopoietic stem and progenitor cell function. Leukemia 28, 227–230 (2014). https://doi.org/10.1038/leu.2013.238

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