Telephone: 61-2-6125-1329; Fax: 61-2-6125-1381
Tissue-Specific Stem Cells
Article first published online: 8 OCT 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 12, pages 3082–3092, December 2009
How to Cite
Papathanasiou, P., Attema, J. L., Karsunky, H., Hosen, N., Sontani, Y., Hoyne, G. F., Tunningley, R., Smale, S. T. and Weissman, I. L. (2009), Self-Renewal of the Long-Term Reconstituting Subset of Hematopoietic Stem Cells Is Regulated by Ikaros. STEM CELLS, 27: 3082–3092. doi: 10.1002/stem.232
Author contributions: P.P.: Conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; J.L.A. and H.K.: Conception and design, collection and assembly of data, data analysis and interpretation, final approval of manuscript; N.H. and G.F.H.: Collection and assembly of data, data analysis and interpretation, final approval of manuscript; Y.S. and R.T.: Collection and assembly of data, final approval of manuscript; S.T.S. and I.L.W.: Financial support, data analysis and interpretation, final approval of manuscript.
First published online in STEM CELLS EXPRESS October 8, 2009.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 14 DEC 2009
- Article first published online: 8 OCT 2009
- Accepted manuscript online: 8 OCT 2009 12:00AM EST
- Manuscript Accepted: 21 SEP 2009
- Manuscript Received: 30 JUL 2009
- NIH. Grant Numbers: 5P01 DK53074, R01 CA086065, R01 DK43726
- National Health & Medical Research Council CJ Martin Fellowship
- and Japanese Society of Promotion of Science Fellowship
- 1Intrinsic and extrinsic control of haematopoietic stem-cell self-renewal. Nature 2008; 453: 306–313..
- 2Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105–111., , et al.
- 3Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 2005; 5: 311–321., .
- 4Stem cells and cancer: Two faces of eve. Cell 2006; 124: 1111–1115., .
- 5Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 2005; 307: 1101–1104., , et al.
- 6FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 2007; 128: 325–339., , et al.
- 7Connecting mammalian genome with phenome by ENU mouse mutagenesis: gene combinations specifying the immune system. Annu Rev Genet 2005; 39: 241–262., .
- 8Trends in large-scale mouse mutagenesis: From genetics to functional genomics. Nat Rev Genet 2008; 9: 803–810..
- 9DNA repair is limiting for haematopoietic stem cells during aging. Nature 2007; 447: 686–690., , et al.
- 10The Ikaros gene is required for the development of all lymphoid lineages. Cell 1994; 79: 143–156., , et al.
- 11Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor. Immunity 2003; 19: 131–144., , et al.
- 12Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proc Natl Acad Sci U S A 1998; 95: 657–662., , et al.
- 13Early hematopoietic lineage restrictions directed by Ikaros. Nat Immunol 2006; 7: 382–391., , et al.
- 14Defects in hematopoietic stem cell activity in Ikaros mutant mice. J Exp Med 1999; 190: 1201–1213., , et al.
- 15The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci U S A 1995; 92: 10302–10306., , et al.
- 16Relative to adult marrow, fetal liver repopulates nearly five times more efficiently long-term than short-term. Exp Hematol 1997; 25: 293–297., , et al.
- 17A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell 1990; 62: 863–874., , et al.
- 18Developing lymph nodes collect CD4+CD3- LTβ+ cells that can differentiate to APC, Nk Cells, And Follicular cells But Not T Or B cells. Immunity 1997; 7: 493–504., , .
- 19Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties. Proc Natl Acad Sci U S A 2007; 104: 5878–5882., , et al.
- 20SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005; 121: 1109–1121., , et al.
- 21Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genetics 2005; 1: e28., , et al.
- 22Purification and characterization of mouse hematopoietic stem cells. Science 1988; 241: 58–62., , .
- 23Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996; 273: 242–245., , et al.
- 24Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells. Proc Natl Acad Sci U S A 2001; 98: 14541–14546., .
- 25Upregulation of Flt3 expression within the bone marrow Lin-Sca1+c-kit+ stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 2001; 15: 659–669., , et al.
- 26Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes Dev 1998; 12: 782–796., , et al.
- 27Eos and pegasus, two members of the Ikaros family of proteins with distinct DNA binding activities. J Biol Chem 2000; 275: 38347–38354., , et al.
- 28Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to regulate lymphocyte differentiation. EMBO J 1997; 16: 2004–2013., , et al.
- 29Ikaros regulates human haemoglobin switching by facilitating developmental stage specific interactions between the individual globin gene promoters and a chromatin hub. Br J Haematol 2008; 141: 398–406., , et al.
- 30Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 1996; 86: 897–906., .
- 31Of lineage and legacy: The development of mammalian hematopoietic stem cells. Nat Immunol 2008; 9: 129–136., .
- 32Evaluation of the long-term reconstituting subset of hematopoietic stem cells with CD150. Stem Cells 2009 Jul 10 (Epub ahead of print)., , et al.
- 33Perturbation of Ikaros isoform selection by MLV integration is a cooperative event in NotchIC-induced T cell leukemogenesis. Cancer Cell 2003; 3: 551–564., .
- 34Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalised by constitutive Notch1 signaling. Nat Med 2000; 6: 1278–1281., , et al.
- 35Induction of T cell development from hematopoietic progenitor cells in vitro. Immunity 2002; 17: 749–756., .
- 36Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes. J Exp Med 1997; 186: 173–182., , et al.
- 37Putative “stemness” gene Jam-B is not required for maintenance of stem cell state in embryonic, neural, or hematopoetic stem cells. Mol Cell Biol 2006; 26: 6557–6570., , et al.
- 38Diversification of stem cell molecular repertoire by alternative splicing. Proc Natl Acad Sci U S A 2005; 102: 14290–14295., , et al.
- 39Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci U S A 2005; 102: 9194–9199., , et al.
- 40Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003; 423: 302–305., , et al.
- 41Bmi-1-green fluorescent protein-knock-in mice reveal the dynamic regulation of bmi-1 expression in normal and leukemic hematopoietic cells. Stem Cells 2007; 25: 1635–1644., , et al.
- 42Ikaros represses the transcriptional response to Notch signaling in T-cell development. Mol Cell Biol 2008; 28: 7465–7475., , et al.
- 43Ikaros regulates Notch target gene expression in developing thymocytes. J Immunol 2008; 181: 6265–6274., .
- 44Ikaros DNA-binding proteins as integral components of B cell developmental-stage-specific regulatory circuits. Immunity 2007; 26: 335–344., , et al.
- 45Chromatin in pluripotent embryonic stem cells and differentiation. Nat Rev Mol Cell Biol 2006; 7: 540–546., .
- 46Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev 1997; 11: 774–785., , et al.
- 47Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell 2002; 3: 137–147., , et al.
- 48Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity 2009; 30: 493–507., , et al.
- 49Proximity among distant regulatory elements at the beta-globin locus requires GATA-1 and FOG-1. Mol Cell 2005; 17: 453–462., , et al.
- 50Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis. Proc Natl Acad Sci U S A 2007; 104: 12371–12376., , et al.