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Control of Self‐Renewal and Differentiation of Hematopoietic Stem Cells: HOXB4 on the Threshold
Author(s) -
KLUMP HANNES,
SCHIEDLMEIER BERNHARD,
BAUM CHRISTOPHER
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1349.002
Subject(s) - haematopoiesis , stem cell , biology , embryonic stem cell , transcription factor , microbiology and biotechnology , progenitor cell , ectopic expression , cellular differentiation , in vitro , in vivo , cancer research , immunology , genetics , cell culture , gene
A bstract : 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.