The Competitive Nature of HOXB4-Transduced HSC Is Limited by PBX1
| Autor: | Nadine Mayotte, R. Keith Humphries, Guy Sauvageau, Jana Krosl, Nathalie Beslu |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
0303 health sciences
Myeloid Immunology Hematopoietic stem cell Biology Endothelial stem cell 03 medical and health sciences Haematopoiesis 0302 clinical medicine medicine.anatomical_structure Infectious Diseases In vivo 030220 oncology & carcinogenesis Cancer research medicine Immunology and Allergy Stem cell Ex vivo 030304 developmental biology |
| Zdroj: | Immunity. 18(4):561-571 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/s1074-7613(03)00090-6 |
| Popis: | We previously showed that HOXB4 is a potent stimulator of hematopoietic stem cell (HSC) proliferation in vivo and ex vivo. As a result, HOXB4 overexpressing HSCs are 20- to 50-times more competitive than untransduced cells when transplanted into mice. By knocking down the expression of PBX1 (PBX1 K.D. ) in HOXB4 overexpressing cells, we now present the possibility of generating HSCs that are >20-times more competitive than those that overexpress HOXB4. The differentiation activity of these cells appears intact, since they competitively contributed to the reconstitution of normal myeloid and lymphoid compartments in vivo. We also show that the in vivo expansion of HOXB4-PBX1 K.D. -expressing HSCs regenerated normal stem cell pools and did not lead to HSC levels above those detected in unmanipulated mice. The vigorous competitive nature of these cells in vivo compared to HOXB4-transduced HSCs suggests the existence of a distinct, non-cell autonomous mechanism that limits the expansion of HOXB4-transduced hemopoietic stem cells in mice. |
| Databáze: | OpenAIRE |
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