Asymmetric Cell Divisions Sustain Long-Term Hematopoiesis from Single-sorted Human Fetal Liver Cells

doi:10.1084/jem.188.6.1117

This Article

	Full Text
	Full Text (PDF, 181K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Brummendorf, T. H.
	Articles by Lansdorp, P. M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Brummendorf, T. H.
	Articles by Lansdorp, P. M.


Social Bookmarking

	What's this?

J. Exp. Med., Volume 188, Number 6, September 21, 1998 1117-1124

Asymmetric Cell Divisions Sustain Long-Term Hematopoiesis from Single-sorted Human Fetal Liver Cells

By Tim H. Brummendorf,^* Wieslawa Dragowska,^* J.Mark J.M. Zijlmans, Gayle Thornbury,^* and Peter M. Lansdorp^*^§

From the ^* Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, V5Z 1L3, Canada; the Institute of Hematology, Erasmus University, 3000 DR, Rotterdam, The Netherlands; and the ^§ Department of Medicine, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada

Hematopoietic stem cells (HSCs) in adult marrow are believed to be derived from fetal liver precursors. To study cell kineticsinvolved in long-term hematopoiesis, we studied single-sortedcandidate HSCs from fetal liver that were cultured in the presenceof a mixture of stimulatory cytokines. After 8-10 d, the numberof cells in primary cultures varied from <100 to >10,000 cells.Single cells in slow growing colonies were recloned upon reachinga 100-200 cell stage. Strikingly, the number of cells in subclonesvaried widely again. These results are indicative of asymmetricdivisions in primitive hematopoietic cells in which proliferativepotential and cell cycle properties are unevenly distributed amongdaughter cells. The continuous generation of functional heterogeneityamong the clonal progeny of HSCs is in support of intrinsic controlof stem cell fate and provides a model for the long-term maintenanceof hematopoiesis in vitro and in vivo.

Key words: asymmetric cell divisions; stem cells; hematopoiesis; cell cycle; long-term hematopoietic cell cultures

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Drummond, M. W., Balabanov, S., Holyoake, T. L., Brummendorf, T. H. (2007). Concise Review: Telomere Biology in Normal and Leukemic Hematopoietic Stem Cells. Stem Cells 25: 1853-1861 [Abstract] [Full Text]
Beckmann, J., Scheitza, S., Wernet, P., Fischer, J. C., Giebel, B. (2007). Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins. Blood 109: 5494-5501 [Abstract] [Full Text]
Balabanov, S., Gontarewicz, A., Ziegler, P., Hartmann, U., Kammer, W., Copland, M., Brassat, U., Priemer, M., Hauber, I., Wilhelm, T., Schwarz, G., Kanz, L., Bokemeyer, C., Hauber, J., Holyoake, T. L., Nordheim, A., Brummendorf, T. H. (2007). Hypusination of eukaryotic initiation factor 5A (eIF5A): a novel therapeutic target in BCR-ABL-positive leukemias identified by a proteomics approach. Blood 109: 1701-1711 [Abstract] [Full Text]
Dykstra, B., Ramunas, J., Kent, D., McCaffrey, L., Szumsky, E., Kelly, L., Farn, K., Blaylock, A., Eaves, C., Jervis, E. (2006). High-resolution video monitoring of hematopoietic stem cells cultured in single-cell arrays identifies new features of self-renewal. Proc. Natl. Acad. Sci. USA 103: 8185-8190 [Abstract] [Full Text]
Giebel, B., Zhang, T., Beckmann, J., Spanholtz, J., Wernet, P., Ho, A. D., Punzel, M. (2006). Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division. Blood 107: 2146-2152 [Abstract] [Full Text]
Wagner, W., Laufs, S., Blake, J., Schwager, C., Wu, X., Zeller, J. W., Ho, A. D., Fruehauf, S. (2005). Retroviral Integration Sites Correlate with Expressed Genes in Hematopoietic Stem Cells. Stem Cells 23: 1050-1058 [Abstract] [Full Text]
Appel, S., Balabanov, S., Brummendorf, T. H., Brossart, P. (2005). Effects of Imatinib on Normal Hematopoiesis and Immune Activation. Stem Cells 23: 1082-1088 [Abstract] [Full Text]
Bartolovic, K., Balabanov, S., Berner, B., Buhring, H.-J., Komor, M., Becker, S., Hoelzer, D., Kanz, L., Hofmann, W.-K., Brummendorf, T. H. (2005). Clonal Heterogeneity in Growth Kinetics of CD34+CD38- Human Cord Blood Cells In Vitro Is Correlated with Gene Expression Pattern and Telomere Length. Stem Cells 23: 946-957 [Abstract] [Full Text]
Srour, E. F., Tong, X., Sung, K. W., Plett, P. A., Rice, S., Daggy, J., Yiannoutsos, C. T., Abonour, R., Orschell, C. M. (2005). Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38-/lo cells in G0. Blood 105: 3109-3116 [Abstract] [Full Text]
Takano, H., Ema, H., Sudo, K., Nakauchi, H. (2004). Asymmetric Division and Lineage Commitment at the Level of Hematopoietic Stem Cells: Inference from Differentiation in Daughter Cell and Granddaughter Cell Pairs. JEM 199: 295-302 [Abstract] [Full Text]
Rollini, P., Kaiser, S., Faes-van't Hull, E., Kapp, U., Leyvraz, S. (2004). Long-term expansion of transplantable human fetal liver hematopoietic stem cells. Blood 103: 1166-1170 [Abstract] [Full Text]
Bartolovic, K., Balabanov, S., Hartmann, U., Komor, M., Boehmler, A. M., Buhring, H.-J., Mohle, R., Hoelzer, D., Kanz, L., Hofmann, W.-K., Brummendorf, T. H. (2004). Inhibitory effect of imatinib on normal progenitor cells in vitro. Blood 103: 523-529 [Abstract] [Full Text]
Forraz, N., Pettengell, R., McGuckin, C. P. (2004). Characterization of a Lineage-Negative Stem-Progenitor Cell Population Optimized for Ex Vivo Expansion and Enriched for LTC-IC. Stem Cells 22: 100-108 [Abstract] [Full Text]
Ho, A. D., Punzel, M. (2003). Hematopoietic stem cells: can old cells learn new tricks?. J. Leukoc. Biol. 73: 547-555 [Abstract] [Full Text]
Hawley, R. G., Sobieski, D. A. (2003). Stem Cell Molecular Blueprint: "Life, the Universe, and Everything". Stem Cells 21: 1-4 [Full Text]
Gordon, M. Y., Lewis, J. L., Marley, S. B. (2002). Of mice and men ... and elephants. Blood 100: 4679-4679 [Full Text]
Aube, M., Lafrance, M., Charbonneau, C., Goulet, I., Carreau, M. (2002). Hematopoietic Stem Cells from Fancc-/- Mice Have Lower Growth and Differentiation Potential in Response to Growth Factors. Stem Cells 20: 438-447 [Abstract] [Full Text]
Wilpshaar, J., Bhatia, M., Kanhai, H. H. H., Breese, R., Heilman, D. K., Johnson, C. S., Falkenburg, J. H. F., Srour, E. F. (2002). Engraftment potential of human fetal hematopoietic cells in NOD/SCID mice is not restricted to mitotically quiescent cells. Blood 100: 120-127 [Abstract] [Full Text]
Mantel, C., Hendrie, P., Broxmeyer, H. E. (2001). Steel Factor Regulates Cell Cycle Asymmetry. Stem Cells 19: 483-491 [Abstract] [Full Text]
Brummendorf, T. H., Maciejewski, J. P., Mak, J., Young, N. S., Lansdorp, P. M. (2001). Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood 97: 895-900 [Abstract] [Full Text]
Oh, I.-H., Lau, A., Eaves, C. J. (2000). During ontogeny primitive (CD34+CD38-) hematopoietic cells show altered expression of a subset of genes associated with early cytokine and differentiation responses of their adult counterparts. Blood 96: 4160-4168 [Abstract] [Full Text]
Glimm, H., Oh, I.-H., Eaves, C. J. (2000). Human hematopoietic stem cells stimulated to proliferate in vitro lose engraftment potential during their S/G2/M transit and do not reenter G0. Blood 96: 4185-4193 [Abstract] [Full Text]
Ema, H., Takano, H., Sudo, K., Nakauchi, H. (2000). In Vitro Self-Renewal Division of Hematopoietic Stem Cells. JEM 192: 1281-1288 [Abstract] [Full Text]
Glimm, H., Eaves, C.J. (1999). Direct Evidence for Multiple Self-Renewal Divisions of Human In Vivo Repopulating Hematopoietic Cells in Short-Term Culture. Blood 94: 2161-2168 [Abstract] [Full Text]
Rufer, N., Brummendorf, T. H., Kolvraa, S., Bischoff, C., Christensen, K., Wadsworth, L., Schulzer, M., Lansdorp, P. M. (1999). Telomere Fluorescence Measurements in Granulocytes and T Lymphocyte Subsets Point to a High Turnover of Hematopoietic Stem Cells and Memory T Cells in Early Childhood. JEM 190: 157-168 [Abstract] [Full Text]
Bennaceur-Griscelli, A., Tourino, C., Izac, B., Vainchenker, W., Coulombel, L. (1999). Murine Stromal Cells Counteract the Loss of Long-Term Culture-Initiating Cell Potential Induced by Cytokines in CD34+CD38low/neg Human Bone Marrow Cells. Blood 94: 529-538 [Abstract] [Full Text]
Case, S. S., Price, M. A., Jordan, C. T., Yu, X. J., Wang, L., Bauer, G., Haas, D. L., Xu, D., Stripecke, R., Naldini, L., Kohn, D. B., Crooks, G. M. (1999). Stable transduction of quiescent CD34+CD38- human hematopoietic cells by HIV-1-based lentiviral vectors. Proc. Natl. Acad. Sci. USA 96: 2988-2993 [Abstract] [Full Text]