Forced expression of HoxB4 enhances hematopoietic differentiation by human embryonic stem cells.
HoxB4 has been shown to enhance hematopoietic engraftment by hematopoietic stem cells (HSC) from differentiating mouse embryonic stem cell (mESC) cultures. Here we examined the effect of ectopic expression of HoxB4 in differentiated human embryonic stem cells (hESCs). Stable HoxB4-expressing hESCs were established by lentiviral transduction, and the forced expression of HoxB4 did not affect stem cell features. HoxB4-expressing hESC-derived CD34+ cells generated higher numbers of erythroid and blast-like colonies than controls. The number of CD34+ cells increased but CD45+ and KDR+ cell numbers were not significantly affected. When the hESC derived CD34+ cells were transplanted into NOD/SCID beta 2m-/- mice, the ectopic expression of HoxB4 did not alter their repopulating capacity. Our findings show that overexpression of HoxB4 in differentiating hESCs increases hematopoietic colony formation and hematopoietic cell formation in vitro, but does not affect in vivo repopulation in adult mice hosts.
Moore Laboratory, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. gabsang@gmail.com
Gab Sang
GS
Lee
Byung Soo
BS
Kim
Jae-Hung
JH
Sheih
Malcolm
M
Moore
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D016086:Lentivirus; D051379:Mice; D016513:Mice, SCID; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic
D018952:Antigens, CD34; C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors