title: The hypomorphic Gata1low mutation alters the proliferation/differentiation potential of the common megakaryocytic-erythroid progenitor.
abstract: Recent evidence suggests that mutations in the Gata1 gene may alter the proliferation/differentiation potential of hemopoietic progenitors. By single-cell cloning and sequential replating experiments of prospectively isolated progenitor cells, we demonstrate here that the hypomorphic Gata1low mutation increases the proliferation potential of a unique class of progenitor cells, similar in phenotype to adult common erythroid/megakaryocytic progenitors (MEPs), but with the "unique" capacity to generate erythroblasts, megakaryocytes, and mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast cell progenitors (MCPs) are not detectable in the marrow from these mutants. At the single-cell level, about 11% of Gata1low progenitor cells, including MEPs, generate cells that will continue to proliferate in cultures for up to 4 months. In agreement with these results, trilineage (erythroid, megakaryocytic, and mastocytic) cell lines are consistently isolated from bone marrow and spleen cells of Gata1low mice. These results confirm the crucial role played by Gata1 in hematopoietic commitment and identify, as a new target for the Gata1 action, the restriction point at which common myeloid progenitors become either MEPs or MCPs.
authors.affiliation: Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ghinassi
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Martelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amabile
authors.forename: Alessandro Maria
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Migliaccio
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Orkin
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Migliaccio
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology*; D050982:GATA1 Transcription Factor / Q000235:genetics*; D008407:Mast Cells / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D009154:Mutation
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human