Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Animals
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Bone Marrow Cells / cytology
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Bone Marrow Cells / metabolism
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Bone Marrow Transplantation / methods
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Cell Culture Techniques / methods*
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Cell Division / drug effects
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Cell Division / physiology*
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Clone Cells / cytology
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Clone Cells / drug effects
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Clone Cells / metabolism
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Female
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / physiology
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Graft Survival / drug effects
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Graft Survival / physiology*
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Hematopoietic Stem Cell Transplantation / methods*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / metabolism*
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Homeodomain Proteins / metabolism*
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Homeodomain Proteins / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Transcription Factors / metabolism*
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Transcription Factors / pharmacology
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Transduction, Genetic / methods
Substances
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Homeodomain Proteins
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Hoxb4 protein, mouse
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Transcription Factors