Genetic control of the frequency of hematopoietic stem cells in mice: mapping of a candidate locus to chromosome 1

doi:10.1084/jem.183.3.1141

This Article

	Full Text (PDF, 1354K)
	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 Muller-Sieburg, C. E.
	Articles by Riblet, R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Muller-Sieburg, C. E.
	Articles by Riblet, R.


Social Bookmarking

	What's this?

ARTICLES

Genetic control of the frequency of hematopoietic stem cells in mice: mapping of a candidate locus to chromosome 1

CE Muller-Sieburg and R Riblet
Medical Biology Institute, La Jolla, California 92037, USA.

The genetic elements that govern the differentiation and proliferation of hematopoietic stem cells remain to be defined. We describe here marked strain-specific differences in the frequency of long-term culture-initiating cells (LTC-IC) in the bone marrow of different strains of mice. Mice of C57Bl/6 background showed the lowest levels of stem cells in marrow, averaging 2.4 +/- .06 LTC-IC/10(5) cells, BALB/c is intermediate (9.1 +/- 4.2/10(5) cells), and DBA/2 mice contained a 11-fold higher frequency of LTC-IC (28.1 +/- 16.5/10(5) cells) than C57Bl/6 mice. The genetic factors affecting the size of the stem cell pool were analyzed in the C57Bl/6 X DBA/2 recombinant inbred strains; LTC-IC frequencies ranged widely, indicating that stem cell frequencies are controlled by multiple genes. Quantitative trait linkage analysis suggested that two loci that have major quantitative effects are located on chromosome 1 near Adprp and Acrg, respectively. The mapping of the locus near Adprp was confirmed by finding an elevated stem cell frequency in B6.C-H25, a C57Bl/6 congenic strain that carries a portion of chromosome 1 derived from BALB/c mice. We have named this gene Scfr1 (stem cell frequency regulator 1). The allelic forms of this gene may be an important predictor of stem cell number and thus would be useful for evaluating cell sources in clinical stem cell transplantation.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Hardwick, R. J., Tretyakov, M. V., Dubrova, Y. E. (2009). Age-Related Accumulation of Mutations Supports a Replication-Dependent Mechanism of Spontaneous Mutation at Tandem Repeat DNA Loci in Mice. Mol Biol Evol 26: 2647-2654 [Abstract] [Full Text]
Avagyan, S., Glouchkova, L., Choi, J., Snoeck, H.-W. (2008). A Quantitative Trait Locus on Chromosome 4 Affects Cycling of Hematopoietic Stem and Progenitor Cells through Regulation of TGF-{beta}2 Responsiveness. J. Immunol. 181: 5904-5911 [Abstract] [Full Text]
Ahuja, A. K., Barber, R. C., Hardwick, R. J., Weil, M. M., Genik, P. C., Brenner, D. J., Dubrova, Y. E. (2008). The effects of Atm haploinsufficiency on mutation rate in the mouse germ line and somatic tissue. Mutagenesis 23: 367-370 [Abstract] [Full Text]
Cho, R. H., Sieburg, H. B., Muller-Sieburg, C. E. (2008). A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 111: 5553-5561 [Abstract] [Full Text]
Jawad, M, Giotopoulos, G, Cole, C, Plumb, M (2007). Target cell frequency is a genetically determined risk factor in radiation leukaemogenesis. Br. J. Radiol. 80: S56-S62 [Abstract] [Full Text]
Jawad, M., Seedhouse, C. H., Russell, N., Plumb, M. (2006). Polymorphisms in human homeobox HLX1 and DNA repair RAD51 genes increase the risk of therapy-related acute myeloid leukemia. Blood 108: 3916-3918 [Abstract] [Full Text]
Sieburg, H. B., Cho, R. H., Dykstra, B., Uchida, N., Eaves, C. J., Muller-Sieburg, C. E. (2006). The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets. Blood 107: 2311-2316 [Abstract] [Full Text]
Catlin, S. N., Guttorp, P., Abkowitz, J. L. (2005). The kinetics of clonal dominance in myeloproliferative disorders. Blood 106: 2688-2692 [Abstract] [Full Text]
Liang, Y., Van Zant, G., Szilvassy, S. J. (2005). Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 106: 1479-1487 [Abstract] [Full Text]
Geiger, H., Rennebeck, G., Van Zant, G. (2005). Regulation of hematopoietic stem cell aging in vivo by a distinct genetic element. Proc. Natl. Acad. Sci. USA 102: 5102-5107 [Abstract] [Full Text]
Muller-Sieburg, C. E., Cho, R. H., Karlsson, L., Huang, J.-F., Sieburg, H. B. (2004). Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood 103: 4111-4118 [Abstract] [Full Text]
Cao, Y.-A., Wagers, A. J., Beilhack, A., Dusich, J., Bachmann, M. H., Negrin, R. S., Weissman, I. L., Contag, C. H. (2004). Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc. Natl. Acad. Sci. USA 101: 221-226 [Abstract] [Full Text]
Langer, J. C., Henckaerts, E., Orenstein, J., Snoeck, H.-W. (2004). Quantitative Trait Analysis Reveals Transforming Growth Factor-{beta}2 as a Positive Regulator of Early Hematopoietic Progenitor and Stem Cell Function. JEM 199: 5-14 [Abstract] [Full Text]
Tang, Y., McKinnon, M. L., Leong, L. M., Rusholme, S. A. B., Wang, S., Akhurst, R. J. (2003). Genetic modifiers interact with maternal determinants in vascular development of Tgfb1-/- mice. Hum Mol Genet 12: 1579-1589 [Abstract] [Full Text]
Boulton, E., Cole, C., Knight, A., Cleary, H., Snowden, R., Plumb, M. (2003). Low-penetrance genetic susceptibility and resistance loci implicated in the relative risk for radiation-induced acute myeloid leukemia in mice. Blood 101: 2349-2354 [Abstract] [Full Text]
de Haan, G., Bystrykh, L. V., Weersing, E., Dontje, B., Geiger, H., Ivanova, N., Lemischka, I. R., Vellenga, E., Van Zant, G. (2002). A genetic and genomic analysis identifies a cluster of genes associated with hematopoietic cell turnover. Blood 100: 2056-2062 [Abstract] [Full Text]
de Guzman, C. G., Warren, A. J., Zhang, Z., Gartland, L., Erickson, P., Drabkin, H., Hiebert, S. W., Klug, C. A. (2002). Hematopoietic Stem Cell Expansion and Distinct Myeloid Developmental Abnormalities in a Murine Model of the AML1-ETO Translocation. Mol. Cell. Biol. 22: 5506-5517 [Abstract] [Full Text]
Muller-Sieburg, C. E., Cho, R. H., Thoman, M., Adkins, B., Sieburg, H. B. (2002). Deterministic regulation of hematopoietic stem cell self-renewal and differentiation. Blood 100: 1302-1309 [Abstract] [Full Text]
Sargent, L. M., Senft, J. R., Lowry, D. T., Jefferson, A. M., Tyson, F. L., Malkinson, A. M., Coleman, A. E., Reynolds, S. H. (2002). Specific Chromosomal Aberrations in Mouse Lung Adenocarcinoma Cell Lines Detected by Spectral Karyotyping: A Comparison with Human Lung Adenocarcinoma. Cancer Res. 62: 1152-1157 [Abstract] [Full Text]
Morrison, S. J., Qian, D., Jerabek, L., Thiel, B. A., Park, I.-K., Ford, P. S., Kiel, M. J., Schork, N. J., Weissman, I. L., Clarke, M. F. (2002). A Genetic Determinant That Specifically Regulates the Frequency of Hematopoietic Stem Cells. J. Immunol. 168: 635-642 [Abstract] [Full Text]
Geiger, H., True, J. M., de Haan, G., Van Zant, G. (2001). Age- and stage-specific regulation patterns in the hematopoietic stem cell hierarchy. Blood 98: 2966-2972 [Abstract] [Full Text]
Chen, J., Astle, C. M., Muller-Sieburg, C. E., Harrison, D. E. (2000). Primitive hematopoietic stem cell function in vivo is uniquely high in the CXB-12 mouse strain. Blood 96: 4124-4131 [Abstract] [Full Text]
de Haan, G., Szilvassy, S. J., Meyerrose, T. E., Dontje, B., Grimes, B., Van Zant, G. (2000). Distinct functional properties of highly purified hematopoietic stem cells from mouse strains differing in stem cell numbers. Blood 96: 1374-1379 [Abstract] [Full Text]
Muller-Sieburg, C. E., Cho, R. H., Sieburg, H. B., Kupriyanov, S., Riblet, R. (2000). Genetic control of hematopoietic stem cell frequency in mice is mostly cell autonomous. Blood 95: 2446-2448 [Abstract] [Full Text]
Cheng, T., Rodrigues, N., Shen, H., Yang, Y., Dombkowski, D., Sykes, M., Scadden, D. T. (2000). Hematopoietic Stem Cell Quiescence Maintained by p21cip1/waf1. Science 287: 1804-1808 [Abstract] [Full Text]
Gerhard, G. S. (1999). Inter-Strain Variation in Murine Models of Leukemia. Blood 94: 1142-1142 [Full Text]
de Haan, G., Van Zant, G. (1999). Dynamic Changes in Mouse Hematopoietic Stem Cell Numbers During Aging. Blood 93: 3294-3301 [Abstract] [Full Text]
DE HAAN, G., VAN ZANT, G. (1999). Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span. FASEB J. 13: 707-713 [Abstract] [Full Text]
Koller, M. R., Manchel, I., Smith, A. K. (1998). Quantitative Long-Term Culture-Initiating Cell Assays Require Accessory Cell Depletion That Can Be Achieved by CD34-Enrichment or 5-Fluorouracil Exposure. Blood 91: 4056-4064 [Abstract] [Full Text]
Haan, G. d., Zant, G. V. (1997). Intrinsic and Extrinsic Control of Hemopoietic Stem Cell Numbers: Mapping of a Stem Cell Gene. JEM 186: 529-536 [Abstract] [Full Text]
Morrison, S. J., Wright, D. E., Weissman, I. L. (1997). Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to�mobilization. Proc. Natl. Acad. Sci. USA 94: 1908-1913 [Abstract] [Full Text]
Morrison, S., Wandycz, A., Hemmati, H., Wright, D., Weissman, I. (1997). Identification of a lineage of multipotent hematopoietic progenitors. Development 124: 1929-1939 [Abstract]