The Hox genes are a family of homeodomain-containing transcription factors which determine anteroposterior identity early on in development. Although a lot is now known about their regulation and function, very little is known of their effector (downstream target) genes. Here we show that the small GTPase Rap1 is a direct, negatively regulated target of Hoxb4 and is excluded from Hoxb4 expressi...

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 determin...

UNLABELLED : We have developed a robust, Good Manufacturing Practice-compatible differentiation protocol capable of producing scalable quantities of red blood cells (RBCs) from human pluripotent stem cells (hPSCs). However, translation of this protocol to the clinic has been compromised because the RBCs produced are not fully mature; thus, they express embryonic and fetal, rather than adult glo...

Hox genes have the interesting property of specifying both spatial identity along the rostrocaudal axis of the developing embryo and differentiation status within the hierarchy of hematopoietic cell fates. Their importance to hematopoiesis is underscored by the overexpression of various Hox genes in hematologic malignancies, alone, as fusion proteins, or as downstream targets of deregulated MLL...

The molecular mechanisms that underlie the favorable effects of thrombopoietin on stem cell survival, self-renewal, and expansion are unknown. On the basis of known effects of HoxB4, HoxA9, and vascular endothelial cell growth factor on stem cells, we explored whether TPO might affect these pathways. We found that TPO enhances the transcription of HoxB4, induces the nuclear localization of HoxA...

cientists in the field of blood cell development have found a protein of expansive abilities. According to two new papers, HoxB4 is able to promote self-renewal of hematopoietic stem cells (HSCs) both in vivo and in vitro. HoxB4 is a homeotic gene whose expression in vivo has been shown previously to enhance HSC regeneration. Now, Jennifer Antonchuk, Guy Sauvageau, and Keith Humphries (Terry Fo...

Little is known about the molecular mechanisms controlling primitive hematopoietic stem cells, especially during embryogenesis. Homeobox genes encode a family of transcription factors that have gained increasing attention as master regulators of developmental processes and recently have been implicated in the differentiation and proliferation of hematopoietic cells. Several Hox homeobox genes a...

Genetic manipulation of hematopoietic stem and progenitor cells is an important tool for experimental and clinical applied hematology. However, techniques that allow for gene targeting, subsequent in vitro selection, and expansion of genetically defined clones are available only for ES cells. Such molecularly defined and, hence, "safe" clones would be highly desirable for somatic gene therapy. ...

The cytosine analogue decitabine alters hematopoietic differentiation. For example, decitabine treatment increases self-renewal of normal hematopoietic stem cells. The mechanisms underlying decitabine-induced shifts in differentiation are poorly understood, but likely relate to the ability of decitabine to deplete the chromatin-modifying enzyme DNA methyltransferase 1 (DNMT1), which plays a cen...