Identification of the Downstream Effector Genes Involved in HOXB4-Induced Expansion of Hematopoietic Progenitor Cells

<p>Overexpression of HOXB4, a member of Homeobox transcription factor family, promotes expansion of hematopoietic stem and progenitor cells both<em>in vivo </em>and <em>in vitro</em>.<em> </em>However, the molecular mechanisms underlying this effect are not well understood. In order to identify direct target genes of HOXB4 in primary murine hematopoietice progenitor cells, we induced HOXB4 function in lineage-negative, murine bone marrow cells, using a tamoxifen-inducibleHOXB4-ER^T2fusion protein. Seventy seven genes with differentially changed expression in early response to HOXB4 have been identified as candidate target genes. Among them, we show that <em>Hemogen</em> (<em>Hemgn</em>), encoding a nuclear protein specifically expressed in hematopoietic stem and progenitor cells, is a direct transcriptional target of HOXB4, and that HOXB4 binds to the promoter region of <em>Hemgn</em>. More importantly, when overexpressed in bone marrowcells, Hemgn<em> </em>promotes expansion of 5-fluorouracil (5-FU) treated bone marrow cells in both liquid and semi-solid cultures, recapitulating the effects of HOXB4. Furthermore, both Hemgn and HOXB4 can protect bone marrow cells from apoptosis. Our results identify an important direct transcriptional target of HOXB4 that can confer expansion of primitive myeloid progenitor cells.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2009

Author dc:creator

• Jiang, Jie

Contributors dc:contributor

• Brian P. Sorrentino, M.D.

• hematopoietic progenitor cells
• Hemgn
• HOXB4
• self-renewal
• Medical Cell Biology
• Medical Sciences
• Medicine and Health Sciences

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/137

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1129