Downstream targets of HOXB4 in a cell line model of primitive hematopoietic progenitor cells

被引:33
作者
Lee, Han M. [1 ]
Zhang, Hui [2 ]
Schulz, Vincent [3 ]
Tuck, David P. [4 ]
Forget, Bernard G. [1 ,2 ]
机构
[1] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA
[4] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
STEM-CELLS; IN-VITRO; SELF-RENEWAL; IMMUNOGLOBULIN SUPERFAMILY; TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; HOMEOBOX GENES; EXPANSION; PROTEINS; OVEREXPRESSION;
D O I
10.1182/blood-2009-11-253872
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Enforced expression of the homeobox transcription factor HOXB4 has been shown to enhance hematopoietic stem cell self-renewal and expansion ex vivo and in vivo. To investigate the downstream targets of HOXB4 in hematopoietic progenitor cells, HOXB4 was constitutively overexpressed in the primitive hematopoietic progenitor cell line EML. Two genome-wide analytical techniques were used: RNA expression profiling using microarrays and chromatin immuno-precipitation (ChIP)-chip. RNA expression profiling revealed that 465 gene transcripts were differentially expressed in KLS (c-Kit(+), Lin(-), Sca-1(+))-EML cells that overexpressed HOXB4 (KLS-EML-HOXB4) compared with control KLS-EML cells that were transduced with vector alone. In particular, erythroid-specific gene transcripts were observed to be highly down-regulated in KLS-EMLHOXB4 cells. ChIP-chip analysis revealed that the promoter region for 1910 genes, such as CD34, Sox4, and B220, were occupied by HOXB4 in KLS-EML-HOXB4 cells. Side-by-side comparison of the ChIP-chip and RNA expression profiling datasets provided correlative information and identified Gp49a and Laptm4b as candidate "stemness-related" genes. Both genes were highly ranked in both dataset lists and have been previously shown to be preferentially expressed in hematopoietic stem cells and down-regulated in mature hematopoietic cells, thus making them attractive candidates for future functional studies in hematopoietic cells. (Blood. 2010;116(5):720-730)
引用
收藏
页码:720 / 730
页数:11
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