Gata1 expression driven by the alternative HS2 enhancer in the spleen rescues the hematopoietic failure induced by the hypomorphic Gata1low mutation
| Autor: | Giovanni Migliaccio, Rosa Alba Rana, Fabrizio Martelli, Barbara Ghinassi, Anna Rita Migliaccio, Mauro Valeri, Yvette van Hensbergen, Alessandro M. Vannucchi, Willem E. Fibbe, Angela Di Baldassarre, Massimo Sanchez, Maria Verrucci, Maria Zingariello |
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| Rok vydání: | 2009 |
| Předmět: |
Hematopoiesis and Stem Cells
Immunology Biology medicine.disease_cause Biochemistry Mice Myeloproliferative Disorders Bone Marrow Stress Physiological medicine Animals GATA1 Transcription Factor Enhancer Regulation of gene expression Mutation GATA1 Cell Biology Hematology Hematopoietic Stem Cells Mice Mutant Strains Haematopoiesis Enhancer Elements Genetic medicine.anatomical_structure Gene Expression Regulation Hematopoiesis Extramedullary Cancer research Bone marrow Stem cell |
| Zdroj: | Blood. 114:2107-2120 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Rigorously defined reconstitution assays developed in recent years have allowed recognition of the delicate relationship that exists between hematopoietic stem cells and their niches. This balance ensures that hematopoiesis occurs in the marrow under steady-state conditions. However, during development, recovery from hematopoietic stress and in myeloproliferative disorders, hematopoiesis occurs in extramedullary sites whose microenvironments are still poorly defined. The hypomorphic Gata1low mutation deletes the regulatory sequences of the gene necessary for its expression in hematopoietic cells generated in the marrow. By analyzing the mechanism that rescues hematopoiesis in mice carrying this mutation, we provide evidence that extramedullary microenvironments sustain maturation of stem cells that would be otherwise incapable of maturing in the marrow. |
| Databáze: | OpenAIRE |
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