We have found in the past 4 years several genes that affect stem cell behaviors: bcl-2 inhibits programmed cell death, and increases HSC numbers and competitiveness in vivo; Wnt 3A and beta-catenin stimulate phenotypic HSC expansion in vitro, and these cells give LTMR upon transplantation; axin (an inhibitor of beta-catenin) blocks HSC proliferation in response to a variety of cytokines; bmi-1 (from Mike Clarke), whose absence prevents fetal liver hematopoiesis spreading to prenatal and postnatal bone marrow; and hTERT, which enforces HSC telomere maintenance through serial HSC transplants. We have begun the analysis of a number of genes with relative or absolute increased expression in LT-HSC vs. progeny (including ST-HSC). Here we plan to test whether our Wnt/beta -catenin/axin results define a manipulatable pathway for HSC self-renewal, and whether other identified (or newly identified) LT-HSC genes or leukemia translocated genes play roles in HSC self-renewal or other HSC behaviors. We plan to expand dramatically our efforts to find, catalogue, and determine cell lineage expression of all LT-HSC (and ST-HSC/MPP and CLP and CMP) transcripts. Finally, using tet-regulatable lentivirus vectors, we will test candidate genes by transfection of HSC, retain aliquots for in vivo hematopoiesis analyses, and co-transplant the rest to allow the whole animal select the most competitive clones. Recloning and retransfection will further limit the genes likely to play key roles in self-renewal. Recloning and retransfection will further limit the genes likely to play key roles in self-renewal, etc. ES cell complete or conditional knock-outs will help define the role of the genes in vivo.
| Sun, Bingyun; Ma, Li; Yan, Xiaowei et al. (2013) N-glycoproteome of E14.Tg2a mouse embryonic stem cells. PLoS One 8:e55722 |
| Bockhorn, Jessica; Yee, Kathy; Chang, Ya-Fang et al. (2013) MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. Breast Cancer Res Treat 137:373-82 |
| Heffner, Garrett C; Clutter, Matthew R; Nolan, Garry P et al. (2011) Novel hematopoietic progenitor populations revealed by direct assessment of GATA1 protein expression and cMPL signaling events. Stem Cells 29:1774-82 |
| Yan, Xiaowei; Ma, Li; Yi, Danielle et al. (2011) A CD133-related gene expression signature identifies an aggressive glioblastoma subtype with excessive mutations. Proc Natl Acad Sci U S A 108:1591-6 |
| Forsberg, E Camilla; Passegué, Emmanuelle; Prohaska, Susan S et al. (2010) Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic stem cells. PLoS One 5:e8785 |
| Jaiswal, Siddhartha; Chao, Mark P; Majeti, Ravindra et al. (2010) Macrophages as mediators of tumor immunosurveillance. Trends Immunol 31:212-9 |
| Inaba, Mayu; Yuan, Hebao; Salzmann, Viktoria et al. (2010) E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells. PLoS One 5:e12473 |
| Ooi, A G Lisa; Karsunky, Holger; Majeti, Ravindra et al. (2009) The adhesion molecule esam1 is a novel hematopoietic stem cell marker. Stem Cells 27:653-61 |
| Papathanasiou, Peter; Attema, Joanne L; Karsunky, Holger et al. (2009) Evaluation of the long-term reconstituting subset of hematopoietic stem cells with CD150. Stem Cells 27:2498-508 |
| Majeti, Ravindra; Becker, Michael W; Tian, Qiang et al. (2009) Dysregulated gene expression networks in human acute myelogenous leukemia stem cells. Proc Natl Acad Sci U S A 106:3396-401 |
Showing the most recent 10 out of 38 publications
