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Transgenic Expression of Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo
Open accessAbstract
Hemopoiesis is regulated in part by survival/apoptosis of hemopoietic stem/progenitor cells. Exogenously added stromal cell-derived factor-1 ((SDF-1)/CXC chemokine ligand (CXCL)12) enhances survival/antiapoptosis of myeloid progenitor cells in vitro. To further evaluate SDF-1/CXCL12 effects on progenitor cell survival, transgenic mice endogenously expressing SDF-1/CXCL12 under a Rous sarcoma virus promoter were produced. Myeloid progenitors (CFU-granulocyte-macrophage, burst-forming unit-erythroid, CFU-granulocyte-erythrocyte-megakaryocyte-monocyte) from transgenic mice were studied for in vitro survival in the context of delayed addition of growth factors. SDF-1-expressing transgenic myeloid progenitors were enhanced in survival and antiapoptosis compared with their wild-type littermate counterparts. Survival-enhancing effects were due to release of low levels of SDF-1/CXCL12 and mediated through CXCR4 and Gαi proteins as determined by ELISA, an antagonist to CXCR4, Abs to CXCR4 and SDF-1, and pertussis toxin. Transgenic effects of low SDF-1/CXCR4 may be due to synergy of SDF-1/CXCL12 with other cytokines; low SDF-1/CXCL12 synergizes with low concentrations of other cytokines to enhance survival of normal mouse myeloid progenitors. Consistent with in vitro results, progenitors from SDF-1/CXCL12 transgenic mice displayed enhanced marrow and splenic myelopoiesis: greatly increased progenitor cell cycling and significant increases in progenitor cell numbers. These results substantiate survival effects of SDF-1/CXCL12, now extended to progenitors engineered to endogenously produce low levels of this cytokine, and demonstrate activity in vivo for SDF-1/CXCL12 in addition to cell trafficking.
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Cited by
Broxmeyer, H. E., Orschell, C. M., Clapp, D. W., Hangoc, G., Cooper, S., Plett, P. A., Liles, W. C., Li, X., Graham-Evans, B., Campbell, T. B., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041385 · Cited by 970
Self-citationKucia, M., Reca, R., Miekus, K., Wanzeck, J., Wojakowski, W., Janowska‐Wieczorek, A., Ratajczak, J., & Ratajczak, M. Z. (2005) · STEM CELLS · doi:10.1634/stemcells.2004-0342 · Cited by 759
CXCR4–SDF-1 Signalling, Locomotion, Chemotaxis and Adhesion
Kucia, M., Jankowski, K., Reca, R., Wysoczynski, M., Bandura, L., Allendorf, D. J., Zhang, J., Ratajczak, J., & Ratajczak, M. Z. (2004) · Journal of Molecular Histology · doi:10.1023/b:hijo.0000032355.66152.b8 · Cited by 698
HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver
Kollet, O., Shivtiel, S., Chen, Y.-Q., Suriawinata, J., Thung, S. N., Dabeva, M. D., Kahn, J., Spiegel, A., Dar, A., Samira, S., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17902 · Cited by 593
Modulation of hematopoietic stem cell homing and engraftment by CD26
Christopherson, K. W., Hangoc, G., Mantel, C. R., & Broxmeyer, H. E. (2004) · Science · doi:10.1126/science.1097071 · Cited by 452
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Metadata
- Authors
- Broxmeyer, H. E., Cooper, S., Kohli, L., Hangoc, G., Lee, Y., Mantel, C., Clapp, D. W., & Kim, C. H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-01-01
- Volume
- 170
- Issue
- 1
- Pages
- 421-429
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1851300844
- Cited by
- 165
- References
- 0
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Transgenic Expression of Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo. https://app.cochat.ai/papers/10.4049/jimmunol.170.1.421
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- Broxmeyer, H. E., Cooper, S., Kohli, L., Hangoc, G., Lee, Y., Mantel, C., Clapp, D. W., & Kim, C. H. (2003). Transgenic Expression of Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo. The Journal of Immunology. https://doi.org/10.4049/jimmunol.170.1.421
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