title: The human granulocyte/macrophage colony-stimulating factor receptor alpha2 isoform influences haemopoietic lineage commitment and divergence.
abstract: A number of alternatively spliced isoforms of haemopoietic growth factor receptors (HGFRs) have been described, but their role in human haemopoiesis remains undetermined. We have investigated the relative expression of the alpha1 and alpha2 isoforms of human granulocyte/macrophage colony-stimulating factor receptor (hGM-CSFR) during haemopoietic cell differentiation, and have shown that both subunits are independently regulated during differentiation of CD34+ human haemopoietic progenitor cells. To further investigate these ex-vivo observations, we established a series of murine FDCP mix cell lines, which, as a consequence of the ectopic expression of alpha1 or alpha2 hGM-CSFR, demonstrated differential differentiation responses to hGM-CSF. In this model system, hGM-CSFR-alpha2-expressing cells showed increased hGM-CSF-mediated erythroid/megakaryocytic differentiation compared with hGM-CSFR-alpha1-expressing cells.
authors.affiliation: Stem Cell and Leukaemia Biology Group, Christie Hospital, Manchester, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Slater
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Dominic G
authors.initials: DG
authors.lastname: Rothwell
authors.forename: Patrick
authors.initials: P
authors.lastname: Baker
authors.forename: Clare M
authors.initials: CM
authors.lastname: Heyworth
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chopra
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D018952:Antigens, CD34 / Q000097:blood; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D015672:Erythroid Precursor Cells / Q000502:physiology; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D016133:Polymerase Chain Reaction / Q000379:methods; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D020033:Protein Isoforms; D012333:RNA, Messenger; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor