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Tissue-Specific Stem Cells
Version of Record 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 online: 14 DEC 2009
- Version of Record 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
Additional supporting information available online.
|STEM_232_sm_suppinfofigS1.tif||36K||Supplementary Figure 1. Clonogenic myeloid colony readout in methylcellulose of 100 plated CMPs (Lin(−/lo)cKit+Sca1-IL7Rα−CD34+FcγR(lo)) FACS-purified from wild-type (+/+) and mutant (Plstc/Plstc) E14.5 FLs.|
|STEM_232_sm_suppinfofigS2.tif||35K||Supplementary Figure 2. Clonogenic myeloid colony readout in methylcellulose of 100 plated Lin(−/lo)cKit+Sca1-IL7Rα−CD34-FcγR(hi) FACS-purified cells from wild-type (+/+) and mutant (Plstc/Plstc) E14.5 FLs.|
|STEM_232_sm_suppinfofigS3.tif||393K||Supplementary Figure 3. Phenotype of Plstc/Plstc embryo and wild-type sibling in yolk sac at E15.5 showing a marked deficit of red cells in the vitelline and umbilical circulation.|
|STEM_232_sm_suppinfofigS4.tif||135K||Supplementary Figure 4. Representative FACS plots of E14.5 fetal liver after 28 days culture on OP9-DL1 (A) and OP9 (B) stromal cell lines.|
|STEM_232_sm_suppinfofigS5.tif||80K||Supplementary Figure 5. Ikaros plays a crucial role in the self-renewal machinery for the ancestral pool of the long-term reconstituting subset of HSCs. E12.5 Plastic homozygotes boast normal numbers of KTLS(CD150+) LT-HSCs which disappear by E14.5-15.5 leaving accumulated numbers of all non-long-term self-renewing cellular subsets, including KTLS(CD150-) cells. Red arrows indicate the other crucial differentiation checkpoints where Ikaros plays an important role: (i) in the cell fate choice of MPPs/LMPPs to become either lymphoid or myeloid cells, Ikaros regulates the lymphoid checkpoint; and (ii) in the choice of CMPs to become GMPs or MEPs, Ikaros regulates the erythroid checkpoint. With several independent lines of evidence emerging that multipotent LT-HSCs may first lose megakaryocyte/erythrocyte potential and that there may be a more intimate and direct connection between these two cell subsets, Ikaros would clearly regulate this early developmental cell fate choice.|
|STEM_232_sm_suppinfotableS1.doc||61K||Table S1. Sequences of primers used to examine gene expression by qRT-PCR in FACS-purified cells in this study|
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