|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 470-477
All-trans retinoic acid enhances the long-term repopulating
activity of cultured hematopoietic stem cells
Louise E. Purton,
Irwin D. Bernstein, and
Steven J. Collins
From the Clinical Research and Human Biology Divisions, Fred
Hutchinson Cancer Research Center, and The Department of Pediatrics,
The University of Washington, Seattle, WA.
The retinoic acid receptor (RAR) agonist, all-trans retinoic acid
(ATRA), is a potent inducer of terminal differentiation of malignant
promyelocytes, but its effects on more primitive hematopoietic
progenitors and stem cells are less clear. We previously reported that
pharmacologic levels (1 µmol) of ATRA enhanced the generation of
colony-forming cell (CFC) and colony-forming unit-spleen (CFU-S) in
liquid suspension cultures of lin c-kit+ Sca-1+ murine hematopoietic precursors. In this study, we further investigated the
effects of ATRA as well as an RAR antagonist, AGN 193109, on the
generation of transplantable cells, including pre-CFU-S, short-term
repopulating stem cells (STRCs), and long-term repopulating stem cells
(LTRCs). ATRA enhanced the ex vivo maintenance and production of
competitive repopulating STRCs and LTRCs from lin c-kit+ Sca-1+ cells cultured in liquid suspension for 14 days. In addition, ATRA prevented the differentiation of these
primitive stem cells into more mature pre-CFU-S during the 14 days of
culture. In marked contrast, lin c-kit+ Sca-1+ cells
cultured with AGN 193109 for 7 days had virtually no short- or
long-term repopulating ability, but displayed an approximately 6-fold
increase in the pre-CFU-S population. The data suggest that the RAR
agonist ATRA enhances the maintenance and self-renewal of short- and
long-term repopulating stem cells. In contrast, the RAR antagonist AGN
193109 abrogates reconstituting ability, most likely by promoting the differentiation of the primitive stem cells. These results imply an
important and unexpected role of retinoids in regulating hematopoietic stem cell differentiation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Safi, G. G. Muramoto, A. B. Salter, S. Meadows, H. Himburg, L. Russell, P. Daher, P. Doan, M. D. Leibowitz, N. J. Chao, et al.
Pharmacological Manipulation of the RAR/RXR Signaling Pathway Maintains the Repopulating Capacity of Hematopoietic Stem Cells in Culture
Mol. Endocrinol.,
February 1, 2009;
23(2):
188 - 201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Chen, B. L. Esplin, K. P. Garrett, R. S. Welner, C. F. Webb, and P. W. Kincade
Retinoids Accelerate B Lineage Lymphoid Differentiation
J. Immunol.,
January 1, 2008;
180(1):
138 - 145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Taschner, C. Koesters, B. Platzer, A. Jorgl, W. Ellmeier, T. Benesch, and H. Strobl
Down-regulation of RXR{alpha} expression is essential for neutrophil development from granulocyte/monocyte progenitors
Blood,
February 1, 2007;
109(3):
971 - 979.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Chute, G. G. Muramoto, J. Whitesides, M. Colvin, R. Safi, N. J. Chao, and D. P. McDonnell
Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells
PNAS,
August 1, 2006;
103(31):
11707 - 11712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Walkley and S. H. Orkin
Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells
PNAS,
June 13, 2006;
103(24):
9057 - 9062.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. Purton, S. Dworkin, G. H. Olsen, C. R. Walkley, S. A. Fabb, S. J. Collins, and P. Chambon
RAR{gamma} is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation
J. Exp. Med.,
May 15, 2006;
203(5):
1283 - 1293.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. D. Nadauld, D. N. Shelton, S. Chidester, H. J. Yost, and D. A. Jones
The Zebrafish Retinol Dehydrogenase, rdh1l, Is Essential for Intestinal Development and Is Regulated by the Tumor Suppressor Adenomatous Polyposis Coli
J. Biol. Chem.,
August 26, 2005;
280(34):
30490 - 30495.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Ferrell, S. T. Dorsam, H. Ohta, R. K. Humphries, M. K. Derynck, C. Haqq, C. Largman, and H. J. Lawrence
Activation of Stem-Cell Specific Genes by HOXA9 and HOXA10 Homeodomain Proteins in CD34+ Human Cord Blood Cells
Stem Cells,
May 1, 2005;
23(5):
644 - 655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Bug, H. Gul, K. Schwarz, H. Pfeifer, M. Kampfmann, X. Zheng, T. Beissert, S. Boehrer, D. Hoelzer, O. G. Ottmann, et al.
Valproic Acid Stimulates Proliferation and Self-renewal of Hematopoietic Stem Cells
Cancer Res.,
April 1, 2005;
65(7):
2537 - 2541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tsuzuki, K. Kitajima, T. Nakano, A. Glasow, A. Zelent, and T. Enver
Cross Talk between Retinoic Acid Signaling and Transcription Factor GATA-2
Mol. Cell. Biol.,
August 1, 2004;
24(15):
6824 - 6836.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Brunner, H. Laumen, P. J. Nielsen, N. Kraut, and T. Wirth
Expression of the Aldehyde Dehydrogenase 2-like Gene Is Controlled by BOB.1/OBF.1 in B Lymphocytes
J. Biol. Chem.,
November 14, 2003;
278(46):
45231 - 45239.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Perrotta, B. Nobili, F. Rossi, M. Criscuolo, A. Iolascon, D. Di Pinto, I. Passaro, L. Cennamo, A. Oliva, and F. Della Ragione
Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition
Blood,
March 15, 2002;
99(6):
2017 - 2022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Kastner, H. J. Lawrence, C. Waltzinger, N. B. Ghyselinck, P. Chambon, and S. Chan
Positive and negative regulation of granulopoiesis by endogenous RAR{alpha}
Blood,
March 1, 2001;
97(5):
1314 - 1320.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Lehmann, C. Paul, and H. Törmä
Retinoid Receptor Expression and Its Correlation to Retinoid Sensitivity in Non-M3 Acute Myeloid Leukemia Blast Cells
Clin. Cancer Res.,
February 1, 2001;
7(2):
367 - 373.
[Abstract]
[Full Text]
|
|
|
|
|
