A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Philip Beer
PROVIDER: E-GEOD-60957 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Homodimerization of Mpl can also be accomplished in the absence of Tpo, by binding of a synthetic ligand (Chemical inducer of dimerization, CID) to a constitutively expressed fusion protein F36VMpl consisting of a ligand binding domain (F36V) and the intracellular signaling domain of Mpl. In contrast to Tpo stimulation, F36VMpl dimerization in human CD34+ progenitor cells generates robust erythropoiesis. Microarray gene expression profiling of progenitors demonstrated that F36VMpl dimerization, but not Tpo, results in upregulation of critical erythroid genes. CD34+ cord blood cells were transduced with F36VMpl-GFP (GFP reporter gene) and cultured on MS-5 stroma for 7 days in the presence of CID, Tpo, Epo or no factors (no CID, negative control). CD34+GFP+ cells were sorted on day 7 and subjected to microarray (n=3 independent experiments).
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