|
|
Blood, 1 February 2006, Vol. 107, No. 3, pp. 1200-1206.
Prepublished online as a Blood First Edition Paper on October 18, 2005; DOI 10.1182/blood-2005-02-0685.
 Previous Article | Next Article 
Submitted February 18, 2005
Accepted September 24, 2005
Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners
Hui Yu, Youzhong Yuan, Hongmei Shen, and Tao Cheng*
Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Stem Cell Biology Laboratory, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
* Corresponding author; email: chengt{at}upmc.edu.
Transplantation-associated stress can compromise the hematopoietic potential of hematopoietic stem cells (HSCs). As a consequence, HSCs may undergo so called "exhaustion" in serial transplant recipients, for which the cellular and molecular bases are not well understood. Hematopoietic exhaustion appears to be accelerated in the absence of p21Cip1/Waf1 (p21), a cyclin-dependent kinase inhibitor (CKI) in irradiated hosts. Our recent study demonstrated that unlike loss of p21, deletion of p18INK4C (p18), a distinct CKI, results in improved long-term engraftment largely owing to increased self-renewing divisions of HSCs in vivo. We show here that HSCs deficient in p18 sustained their competitiveness to wild-type HSCs from unmanipulated young mice, and retained multilineage differentiation potential after multiple rounds of serial bone marrow transfer over a period of more than 3 years. Further, p18 absence significantly decelerated hematopoietic exhaustion caused by p21 deficiency. Such an effect was shown to occur at the stem cell level, likely by a counteracting mechanism against the cellular senescence outcome. Our current study provides new insights into the distinct impacts of these cell cycle regulators on HSC exhaustion and possibly HSC aging as well under proliferative stress, thereby offering potential pharmacological targets for sustaining the durability of stressed HSCs in transplant or elderly patients.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
X. Hu, H. Shen, C. Tian, H. Yu, G. Zheng, R. XuFeng, Z. Ju, J. Xu, J. Wang, and T. Cheng
Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced leukemia model
Blood,
October 29, 2009;
114(18):
3783 - 3792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-W. Kim, B.-K. Koo, H.-W. Jeong, M.-J. Yoon, R. Song, J. Shin, D.-C. Jeong, S.-H. Kim, and Y.-Y. Kong
Defective Notch activation in microenvironment leads to myeloproliferative disease
Blood,
December 1, 2008;
112(12):
4628 - 4638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yoshida, I. Hazan, J. Zhang, S. Y. Ng, T. Naito, H. J. Snippert, E. J. Heller, X. Qi, L. N. Lawton, C. J. Williams, et al.
The role of the chromatin remodeler Mi-2{beta} in hematopoietic stem cell self-renewal and multilineage differentiation
Genes & Dev.,
May 1, 2008;
22(9):
1174 - 1189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Kent, M. Copley, C. Benz, B. Dykstra, M. Bowie, and C. Eaves
Regulation of Hematopoietic Stem Cells by the Steel Factor/KIT Signaling Pathway
Clin. Cancer Res.,
April 1, 2008;
14(7):
1926 - 1930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-Y. Jang and S. J. Sharkis
A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche
Blood,
October 15, 2007;
110(8):
3056 - 3063.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Berthet, M. C. Rodriguez-Galan, D. L. Hodge, J. Gooya, V. Pascal, H. A. Young, J. Keller, R. Bosselut, and P. Kaldis
Hematopoiesis and Thymic Apoptosis Are Not Affected by the Loss of Cdk2
Mol. Cell. Biol.,
July 15, 2007;
27(14):
5079 - 5089.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
