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| Subject | Predicate | Object |
|---|---|---|
| http://purl.uniprot.org/citations/16089502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16089502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16089502 | http://www.w3.org/2000/01/rdf-schema#comment | "Although several reports have characterized the hematopoietic stem cell (HSC) transcriptome, the roles of HSC-specific genes in hematopoiesis remain elusive. To identify candidate regulators of HSC fate decisions, we compared the transcriptome of human umbilical cord blood and bone marrow (CD34+)(CD33-)(CD38-)Rho(lo)(c-kit+) cells, enriched for hematopoietic stem/progenitor cells with (CD34+)(CD33-)(CD38-)Rho(hi) cells, enriched in committed progenitors. We identified 277 differentially expressed transcripts conserved in these ontogenically distinct cell sources. We next performed a morpholino antisense oligonucleotide (MO)-based functional screen in zebrafish to determine the hematopoietic function of 61 genes that had no previously known function in HSC biology and for which a likely zebrafish ortholog could be identified. MO knock down of 14/61 (23%) of the differentially expressed transcripts resulted in hematopoietic defects in developing zebrafish embryos, as demonstrated by altered levels of circulating blood cells at 30 and 48 h postfertilization and subsequently confirmed by quantitative RT-PCR for erythroid-specific hbae1 and myeloid-specific lcp1 transcripts. Recapitulating the knockdown phenotype using a second MO of independent sequence, absence of the phenotype using a mismatched MO sequence, and rescue of the phenotype by cDNA-based overexpression of the targeted transcript for zebrafish spry4 confirmed the specificity of MO targeting in this system. Further characterization of the spry4-deficient zebrafish embryos demonstrated that hematopoietic defects were not due to more widespread defects in the mesodermal development, and therefore represented primary defects in HSC specification, proliferation, and/or differentiation. Overall, this high-throughput screen for the functional validation of differentially expressed genes using a zebrafish model of hematopoiesis represents a major step toward obtaining meaningful information from global gene profiling of HSCs."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pbio.0030254"xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Flynn C.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Flynn C.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Grindle S.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Grindle S.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Wang T.F."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Wang T.F."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Ekker S.C."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Ekker S.C."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Verfaillie C.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Verfaillie C.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Eckfeldt C.E."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Eckfeldt C.E."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Mendenhall E.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Mendenhall E.M."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Pickart M.A."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/author | "Pickart M.A."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/name | "PLoS Biol."xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/name | "PLoS Biol"xsd:string |
| http://purl.uniprot.org/citations/16089502 | http://purl.uniprot.org/core/pages | "e254"xsd:string |