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S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release
Open accessAbstract
The mechanisms of hematopoietic progenitor cell egress and clinical mobilization are not fully understood. Herein, we report that in vivo desensitization of Sphingosine-1-phosphate (S1P) receptors by FTY720 as well as disruption of S1P gradient toward the blood, reduced steady state egress of immature progenitors and primitive Sca-1+/c-Kit+/Lin− (SKL) cells via inhibition of SDF-1 release. Administration of AMD3100 or G-CSF to mice with deficiencies in either S1P production or its receptor S1P1, or pretreated with FTY720, also resulted in reduced stem and progenitor cell mobilization. Mice injected with AMD3100 or G-CSF demonstrated transient increased S1P levels in the blood mediated via mTOR signaling, as well as an elevated rate of immature c-Kit+/Lin− cells expressing surface S1P1 in the bone marrow (BM). Importantly, we found that S1P induced SDF-1 secretion from BM stromal cells including Nestin+ mesenchymal stem cells via reactive oxygen species (ROS) signaling. Moreover, elevated ROS production by hematopoietic progenitor cells is also regulated by S1P. Our findings reveal that the S1P/S1P1 axis regulates progenitor cell egress and mobilization via activation of ROS signaling on both hematopoietic progenitors and BM stromal cells, and SDF-1 release. The dynamic cross-talk between S1P and SDF-1 integrates BM stromal cells and hematopoeitic progenitor cell motility.
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Cites
Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. (2004) · Nature · doi:10.1038/nature02989 · Cited by 1,175
Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis
Ishii, M., Egen, J. G., Klauschen, F., Meier-Schellersheim, M., Saeki, Y., Vacher, J., Proia, R. L., & Germain, R. N. (2009) · Nature · doi:10.1038/nature07713 · Cited by 515
Cited by
Metabolic regulation of stem cell function in tissue homeostasis and organismal ageing
Chandel, N. S., Jasper, H., Ho, T. T., & Passegué, E. (2016) · Nature Cell Biology · doi:10.1038/ncb3385 · Cited by 326
Finding a way out: S1P signaling and immune cell migration
Baeyens, A. A. L., & Schwab, S. R. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-081519-083952 · Cited by 123
Blood on the tracks: hematopoietic stem cell-endothelial cell interactions in homing and engraftment
Perlin, J. R., Sporrij, A., & Zon, L. I. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1559-8 · Cited by 52
Lü, M.-H., Hu, C.-J., Chen, L., Peng, X., Chen, J., Hu, J.-Y., Teng, M., & Liang, G.-P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068972 · Cited by 43
Metadata
- Authors
- Golan, K., Vagima, Y., Ludin, A., Itkin, T., Cohen-Gur, S., Kalinkovich, A., Kollet, O., Kim, C., Schajnovitz, A., Ovadya, Y., Lapid, K., Shivtiel, S., Morris, A. J., Ratajczak, M. Z., & Lapidot, T.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-03-15
- Volume
- 119
- Issue
- 11
- Pages
- 2478-2488
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2063142068
- Cited by
- 202
- References
- 2
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release. https://app.cochat.ai/papers/10.1182/blood-2011-06-358614
- The paper
- Golan, K., Vagima, Y., Ludin, A., Itkin, T., Cohen-Gur, S., Kalinkovich, A., Kollet, O., Kim, C., Schajnovitz, A., Ovadya, Y., Lapid, K., Shivtiel, S., Morris, A. J., Ratajczak, M. Z., & Lapidot, T. (2012). S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release. Blood. https://doi.org/10.1182/blood-2011-06-358614
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