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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1460-1471.
Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-07-030726.
Previous Article | Next Article 
Submitted July 13, 2006
Accepted September 19, 2006
The hypomorphic Gata1low mutation alters the
proliferation/differentiation potential of the common
megakaryocytic-erythroid progenitor
Barbara Ghinassi, Massimo Sanchez, Fabrizio Martelli, Giovanni Amabile, Alessandro Maria Vannucchi, Giovanni Migliaccio, Stuart H Orkin, and Anna Rita Migliaccio*
Department of Biomorphology, University G. D'Annunzio, Chieti, Italy
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy
Department of Hematology and Oncology, University of Florence, Florence, Italy
Department of Pediatric Oncology, Children's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA
Department of Pathology, University of Illinois at Chicago, Chicago, IL
* Corresponding author; email: migliar{at}iss.it.
Recent evidence suggests that mutations in the Gata1 gene may alter the proliferation/differentiation potential of the 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 (MEP), but with the "unique" capacity to generate erythroblasts, megakaryocytes and mast cells in vitro. Conversely, progenitor cells phenotypically similar to mast cell progenitors (MCP) are not detectable in the marrow from these mutants. At the single cell level, ~11% of Gata1low progenitor cells, including MEP, generate cells that will continue to proliferate in cultures for up to 4 months. In agreement with these results, tri-lineage (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 CMP became either MEP or MCP.

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