title: Control of self-renewal and differentiation of hematopoietic stem cells: HOXB4 on the threshold.
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.
authors.affiliation: Department of Hematology, Hemostaseology, and Oncology, Laboratory of Experimental Cell Therapy (LECT), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. klump.hannes@mh-hannover.de
authors.forename: Hannes
authors.initials: H
authors.lastname: Klump
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schiedlmeier
authors.forename: Christopher
authors.initials: C
authors.lastname: Baum
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D005801:Genes, Homeobox; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological
chemical_list: D018398:Homeodomain Proteins