Published 4 November 2002. doi:10.1084/jem.20010916
© Rockefeller University Press,
0022-1007/2002/11/1141 $5.00
The Journal of Experimental Medicine, Volume 196, Number 9, 1141-1150
Changes in the Proliferative Activity of Human Hematopoietic Stem Cells in NOD/SCID Mice and Enhancement of Their Transplantability after In Vivo Treatment with Cell Cycle Inhibitors
J. Cashman1,2,
B. Dykstra1,
I. Clark-Lewis3,
A. Eaves1,4,5 and
C. Eaves1,2,4,5
1 Terry Fox Laboratory, British Columbia Cancer Agency
2 Department of Medical Genetics, University of British Columbia, Vancouver, BC V5Z 1L3, Canada
3 Department of Biochemistry and the Biomedical Research Centre, University of British Columbia, Vancouver, BC V5Z 1L3, Canada
4 Department of Medicine, University of British Columbia, Vancouver, BC V5Z 1L3, Canada
5 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V5Z 1L3, Canada
Address correspondence to Dr. C. Eaves, Terry Fox Laboratory, 601 West 10th Ave., Vancouver, BC V5Z 1L3, Canada. Phone: 604-877-6070; Fax: 604-877-0712; E-mail: ceaves{at}bccancer.bc.ca
Human hematopoietic tissue contains rare stem cells with multilineage reconstituting ability demonstrable in receptive xenogeneic hosts. We now show that within 3 wk nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice transplanted with human fetal liver cells regenerate near maximum levels of daughter human hematopoietic stem cells (HSCs) able to repopulate secondary NOD/SCID mice. At this time, most of the human HSCs (and other primitive progenitors) are actively proliferating as shown by their sensitivity to treatments that kill cycling cells selectively (e.g., exposure to high specific-activity [3H]thymidine in vitro or 5-fluorouracil in vivo). Interestingly, the proliferating human HSCs were rapidly forced into quiescence by in vivo administration of stromal-derived factor-1 (SDF-1) and this was accompanied by a marked increase in the numbers of human HSCs detectable. A similar result was obtained when transforming growth factor-ß was injected, consistent with a reversible change in HSCs engrafting potential linked to changes in their cell cycle status. By 12 wk after transplant, most of the human HSCs had already entered Go and treatment with SDF-1 had no effect on their engrafting activity. These findings point to the existence of novel mechanisms by which inhibitors of HSC cycling can regulate the engrafting ability of human HSCs executing self-renewal divisions in vivo.
Key Words: TGF-ß SDF-1 cell cycle stem cells engraftment

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
-
Hills, M., Lucke, K., Chavez, E. A., Eaves, C. J., Lansdorp, P. M.
(2009). Probing the mitotic history and developmental stage of hematopoietic cells using single telomere length analysis (STELA). Blood
113: 5765-5775
[Abstract]
[Full Text]
-
Tipping, A. J., Pina, C., Castor, A., Hong, D., Rodrigues, N. P., Lazzari, L., May, G. E., Jacobsen, S. E. W., Enver, T.
(2009). High GATA-2 expression inhibits human hematopoietic stem and progenitor cell function by effects on cell cycle. Blood
113: 2661-2672
[Abstract]
[Full Text]
-
Chabanon, A., Desterke, C., Rodenburger, E., Clay, D., Guerton, B., Boutin, L., Bennaceur-Griscelli, A., Pierre-Louis, O., Uzan, G., Abecassis, L., Bourgeade, M.-F., Lataillade, J.-J., Le Bousse-Kerdiles, M.-C.
(2008). A Cross-Talk Between Stromal Cell-Derived Factor-1 and Transforming Growth Factor-{beta} Controls the Quiescence/Cycling Switch of CD34+ Progenitors Through FoxO3 and Mammalian Target of Rapamycin. Stem Cells
26: 3150-3161
[Abstract]
[Full Text]
-
Yahata, T., Muguruma, Y., Yumino, S., Sheng, Y., Uno, T., Matsuzawa, H., Ito, M., Kato, S., Hotta, T., Ando, K.
(2008). Quiescent Human Hematopoietic Stem Cells in the Bone Marrow Niches Organize the Hierarchical Structure of Hematopoiesis. Stem Cells
26: 3228-3236
[Abstract]
[Full Text]
-
Zhang, C. C., Kaba, M., Iizuka, S., Huynh, H., Lodish, H. F.
(2008). Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation. Blood
111: 3415-3423
[Abstract]
[Full Text]
-
Graham, S. M., Vass, J. K., Holyoake, T. L., Graham, G. J.
(2007). Transcriptional Analysis of Quiescent and Proliferating CD34+ Human Hemopoietic Cells from Normal and Chronic Myeloid Leukemia Sources. Stem Cells
25: 3111-3120
[Abstract]
[Full Text]
-
Yahata, T., Yumino, S., Seng, Y., Miyatake, H., Uno, T., Muguruma, Y., Ito, M., Miyoshi, H., Kato, S., Hotta, T., Ando, K.
(2006). Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells. Blood
108: 2446-2454
[Abstract]
[Full Text]
-
Passegue, E., Wagers, A. J., Giuriato, S., Anderson, W. C., Weissman, I. L.
(2005). Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. JEM
202: 1599-1611
[Abstract]
[Full Text]
-
Lapidot, T., Dar, A., Kollet, O.
(2005). How do stem cells find their way home?. Blood
106: 1901-1910
[Abstract]
[Full Text]
-
Glimm, H., Schmidt, M., Fischer, M., Schwarzwaelder, K., Wissler, M., Klingenberg, S., Prinz, C., Waller, C. F., Lange, W., Eaves, C. J., von Kalle, C.
(2005). Efficient marking of human cells with rapid but transient repopulating activity in autografted recipients. Blood
106: 893-898
[Abstract]
[Full Text]
-
Kahn, J., Byk, T., Jansson-Sjostrand, L., Petit, I., Shivtiel, S., Nagler, A., Hardan, I., Deutsch, V., Gazit, Z., Gazit, D., Karlsson, S., Lapidot, T.
(2004). Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation. Blood
103: 2942-2949
[Abstract]
[Full Text]