HOXB4-induced expansion of adult hematopoietic stem cells ex vivo.
Hox transcription factors have emerged as important regulators of primitive hematopoietic cell proliferation and differentiation. In particular, HOXB4 appears to be a strong positive regulator of hematopoietic stem cell (HSC) self-renewal. Here we demonstrate the potency of HOXB4 to enable high-level ex vivo HSC expansion. Cultures of nontransduced or GFP-transduced murine bone marrow cells experienced large HSC losses over 10-14 days. In sharp contrast, cultures of HOXB4-transduced cells achieved rapid, extensive, and highly polyclonal HSC expansions, resulting in over 1000-fold higher levels relative to controls and a 40-fold net HSC increase. Importantly, these HSCs retained full lympho-myeloid repopulating potential and enhanced in vivo regenerative potential, demonstrating the feasibility of achieving significant ex vivo expansion of HSCs without functional impairment.
Antonchuk
Jennifer
J
Terry Fox Laboratory, British Columbia Cancer Agency, 601 West 10th Avenue, V5Z 1L3, Vancouver, British Columbia, Canada.
Sauvageau
Guy
G
Humphries
R Keith
RK
D000367:Age Factors; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D014161:Transduction, Genetic / Q000379:methods
D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D014157:Transcription Factors