The search for genes active in HSC fate determination has not yet turned up candidate genes and candidate pathways that will explain HSC self-renewal. This project has 4 specific aims to address this issue. First, a highly reproducible method for assaying embryonic stem (ES) cell/lines in vitro and in vivo for hematopoietic and HSC fates has been developed and will be tested and optimized for multiple vs single gene transductions. Second, RT-PCR and immunostaining assays for expression of gene transcripts and gene products in each HSC subset (long-term [LT], short-term [ST], and nonself-renewing multipotent progenitors [MPP] at the single cell level will be used to screen known and yet-to-be identified candidate genes for biological testing. Third, the Li and Cohen dominant negative approach for gene discovery will be used in the ES cell assays described in the first aim to identify new candidates that regulate HSCs and hematopoiesis. Finally, an efficient, high- throughput gene transduced protocol derived from the first aim will be put in place to test the potential of candidate genes to modify HSC behavior, the candidate gene deriving from this project~s aims 2 and 3, and the other 3 projects in this PPG (Hood Clarke, Fuller).
| 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 |
| 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 |
| 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 |
| 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 |
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