Control of Self-Renewal and Differentiation of Hematopoietic Stem Cells: HOXB4 on the Threshold

Authors

  • HANNES KLUMP,

    Corresponding author
    1. Department of Hematology, Hemostasteology, and Oncology, Laboratory for Experimental Cell Therapy (LECT), Hannover Medical School, 30625 Hannover, Germany
    • Address for correspondence: Hannes Klump, Ph.D., Department of Hematology, Hemostaseology, and Oncology, Laboratory of Experimental Cell Therapy (LECT), OE 6862, Transplantation Research Center (TPFZ), K11, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Voice: +49-511-5326062; fax: +49-511-5326987. klump.hannes@mh-hannover.de

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  • BERNHARD SCHIEDLMEIER,

    1. Department of Hematology, Hemostasteology, and Oncology, Laboratory for Experimental Cell Therapy (LECT), Hannover Medical School, 30625 Hannover, Germany
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  • CHRISTOPHER BAUM

    1. Department of Hematology, Hemostasteology, and Oncology, Laboratory for Experimental Cell Therapy (LECT), Hannover Medical School, 30625 Hannover, Germany
    2. Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
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Abstract

Abstract: The homeodomain transcription factor HOXB4 is one of the most attractive tools to expand hematopoietic stem cells in vitro and in vivo and to promote the formation of hematopoietic cells from in vitro differentiated embryonic stem cells. However, the expression levels compatible with the favorable effect of enhanced self-renewal without perturbing differentiation, in vivo, remain to be determined. In this paper, we discuss the necessity to define the “therapeutic width” of HOXB4 expression, based on observations from our lab and others that demonstrate that ectopic HOXB4 expression leads to a concentration-dependent perturbation of lineage differentiation of mouse and human hematopoietic cells. In summary, the combined results argue in favor of the existence of certain threshold levels for HOXB4 activity that control the differentiation and self-renewal behavior of hematopoietic stem and progenitor cells. Indeed, existing evidence suggests that dosage effects of ectopically expressed transcription factors may be more the rule than an exception.

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