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Transforming growth factor beta 1 directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells
Open accessAbstract
Hematopoiesis appears to be regulated, in part, by a balance between extracellular positive and negative growth signals. Transforming growth factor beta-1 (TGF-beta 1) has been shown to be a negative regulator of primitive hematopoietic cells. This study examined the direct effect of TGF-beta 1 on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC) in vitro. We previously reported a cell fractionation approach that includes the selection of low Hoescht 33342/low Rhodamine 123 (low Ho/Rh) cell fractions that are highly enriched for long-term repopulating cells (LTR-HSC) and also clone to a very high efficiency in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6: 90% to 100% of individually cultured low Ho/Rh cells formed high proliferative potential clones. This high cloning efficiency of an LTR-HSC enriched cell population enabled proliferation inhibition studies to be more easily interpreted. In this report, we show that the continuous presence of TGF-beta 1 directly inhibits the cell division of essentially all low Ho/Rh cells (in a dose-dependent manner) during their 0 to 5th cell division in vitro. Therefore, it follows that TGF-beta 1 must directly inhibit the proliferation of LTR-HSC contained within these low Ho/Rh cells. The time required for some low Ho/Rh cells to undergo their first cell division in vitro was also prolonged in the presence of TGF-beta 1. Furthermore, when low Ho/Rh cells were exposed to TFG-beta 1 for varying lengths of time before neutralization of the TGF-beta 1 by monoclonal antibody, the ability to form macroclones was markedly decreased after approximately 4 days of TGF-beta 1 exposure. In addition, 1 to 10 ng/mL of TGF-beta 1 resulted in a maintenance of high proliferative potential-colony-forming cell (HPP-CFC) during 8 days of culture compared with loss of HPP-CFC in cultures with no added TGF- beta 1. In conclusion, this study shows that TGF-beta 1 directly inhibits the initial stages of proliferation of LTR-HSC and appears to slow the differentiation of daughter cells of low Ho/Rh cells.
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Citations
Cited by
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Chambers, S. M., Shaw, C. A., Gatza, C., Fisk, C. J., Donehower, L. A., & Goodell, M. A. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050201 · Cited by 731
Abnormal angiogenesis but intact hematopoietic potential in TGF‐β type I receptor‐deficient mice
Larsson, J., Goumans, M., Sjöstrand, L. J., van Rooijen, M. A., Ward, D., Levéen, P., Xu, X., ten Dijke, P., Mummery, C. L., & Karlsson, S. (2001) · The EMBO Journal · doi:10.1093/emboj/20.7.1663 · Cited by 563
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Blank, U., Karlsson, G., & Karlsson, S. (2008) · Blood · doi:10.1182/blood-2007-07-075168 · Cited by 355
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Metadata
- Authors
- Sitnicka, E., Ruscetti, F., Priestley, G., Wolf, N., & Bartelmez, S.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1996-07-01
- Volume
- 88
- Issue
- 1
- Pages
- 82-88
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2417869212
- Cited by
- 208
- References
- 0
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Sitnicka, E., Ruscetti, F., Priestley, G., Wolf, N., & Bartelmez, S. (1996). Transforming growth factor beta 1 directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells. Blood. https://doi.org/10.1182/blood.v88.1.82.82
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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