title: A population of hematopoietic stem cells derives from GATA4-expressing progenitors located in the placenta and lateral mesoderm of mice.
abstract: GATA transcription factors are expressed in the mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouseGata4gene directs its expression throughout the lateral mesoderm and the allantois, beginning at embryonic day 7.5, becoming restricted to the septum transversum by embryonic day 10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4Cre;R26REYFPmouse line. We found a substantial number of YFP+hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos. Fetal CD41+/cKit+/CD34+and Lin-/cKit+/CD31+YFP+hematopoietic progenitors were much more abundant in the placenta than in the aorta-gonad-mesonephros area. They were clonogenic in the MethoCult assay and fully reconstituted hematopoiesis in myeloablated mice. YFP+cells represented about 20% of the hematopoietic system of adult mice. Adult YFP+hematopoietic stem cells constituted a long-term repopulating, transplantable population. Thus, a lineage of adult hematopoietic stem cells is characterized by the expression of GATA4 in their embryonic progenitors and probably by its extraembryonic (placental) origin, although GATA4 appeared not to be required for hematopoietic stem cell differentiation. Both lineages basically showed similar physiological behavior in normal mice, but clinically relevant properties of this particular hematopoietic stem cell population should be checked in physiopathological conditions.
authors.affiliation: Department of Animal Biology, University of Málaga, Spain.|Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Málaga, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cañete
authors.affiliation: Department of Animal Biology, University of Málaga, Spain.|Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Málaga, Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Carmona
authors.affiliation: Department of Animal Biology, University of Málaga, Spain.|Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Málaga, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ariza
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas (CSIC), Universidad Pablo de Olavide (UPO), Seville, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: Andalusian Center of Molecular Biology and Regenerative Medicine (CABIMER) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas-CIBERDEM, Seville, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: Rojas
authors.affiliation: Department of Animal Biology, University of Málaga, Spain chapuli@uma.es.|Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Málaga, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Muñoz-Chápuli
mesh_terms: D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D016130:Immunophenotyping; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy
chemical_list: D015415:Biomarkers; D050991:GATA4 Transcription Factor