TY - JOUR
T1 - Genome-wide analysis of target genes regulated by HoxB4 in hematopoietic stem and progenitor cells developing from embryonic stem cells
AU - Oshima, Motohiko
AU - Endoh, Mitsuhiro
AU - Endo, Takaho A.
AU - Toyoda, Tetsuro
AU - Nakajima-Takagi, Yaeko
AU - Sugiyama, Fumihiro
AU - Koseki, Haruhiko
AU - Kyba, Michael
AU - Iwama, Atsushi
AU - Osawa, Mitsujiro
PY - 2011/4/14
Y1 - 2011/4/14
N2 - Forced expression of the transcription factor HoxB4 has been shown to enhance the self-renewal capacity of mouse bone marrow hematopoietic stem cells (HSCs) and confer a long-term repopulating capacity to yolk sac and embryonic stem (ES) cell-derived hematopoietic precursors. The fact that ES cell-derived precursors do not repopulate bone marrow without HoxB4 underscores an important role for HoxB4 in the maturation of ES-derived hematopoietic precursors into long-term repopulating HSCs. However, the precise molecular mechanism underlying this process is barely understood. In this study, we performed a genome-wide analysis of HoxB4 using ES cell-derived hematopoietic stem/progenitor cells. The results revealed many of the genes essential for HSC development to be direct targets of HoxB4, such as Runx1, Scl/Tal1, Gata2, and Gfi1. The expression profiling also showed that HoxB4 indirectly affects the expression of several important genes, such as Lmo2, Erg, Meis1, Pbx1, Nov, AhR, and Hemgn. HoxB4 tended to activate the transcription, but the downregulation of a significant portion of direct targets suggested its function to be context-dependent. These findings indicate that HoxB4 reprograms a set of key regulator genes to facilitate the maturation of developing HSCs into repopulating cells. Our list of HoxB4 targets also provides novel candidate regulators for HSCs.
AB - Forced expression of the transcription factor HoxB4 has been shown to enhance the self-renewal capacity of mouse bone marrow hematopoietic stem cells (HSCs) and confer a long-term repopulating capacity to yolk sac and embryonic stem (ES) cell-derived hematopoietic precursors. The fact that ES cell-derived precursors do not repopulate bone marrow without HoxB4 underscores an important role for HoxB4 in the maturation of ES-derived hematopoietic precursors into long-term repopulating HSCs. However, the precise molecular mechanism underlying this process is barely understood. In this study, we performed a genome-wide analysis of HoxB4 using ES cell-derived hematopoietic stem/progenitor cells. The results revealed many of the genes essential for HSC development to be direct targets of HoxB4, such as Runx1, Scl/Tal1, Gata2, and Gfi1. The expression profiling also showed that HoxB4 indirectly affects the expression of several important genes, such as Lmo2, Erg, Meis1, Pbx1, Nov, AhR, and Hemgn. HoxB4 tended to activate the transcription, but the downregulation of a significant portion of direct targets suggested its function to be context-dependent. These findings indicate that HoxB4 reprograms a set of key regulator genes to facilitate the maturation of developing HSCs into repopulating cells. Our list of HoxB4 targets also provides novel candidate regulators for HSCs.
UR - http://www.scopus.com/inward/record.url?scp=79954595962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954595962&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-12-323212
DO - 10.1182/blood-2010-12-323212
M3 - Article
C2 - 21343615
AN - SCOPUS:79954595962
SN - 0006-4971
VL - 117
SP - e142-e150
JO - Blood
JF - Blood
IS - 15
ER -