Functional and molecular analysis of hematopoietic progenitors derived from the aorta-gonad-mesonephros region of the mouse embryo.
Herein, we show that CD34, c-kit double-positive (CD34(+)c-kit(+)) cells from the aorta-gonad-mesonephros (AGM) region of the developing mouse are multipotent in vitro and can undergo both B-lymphoid and multimyeloid differentiation. Molecular analysis of individual CD34(+)c-kit(+) cells by single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) shows coactivation of erythroid (beta-globin) and myeloid (myeloperoxidase [MPO]) but not lymphoid-affiliated (CD3, Thy-1, and lambda5) genes. Additionally, most cells coexpress the stem cell-associated transcriptional regulators AML-1, PU.1, GATA-2 and Lmo2, as well as the granulocyte colony-stimulating factor receptor (G-CSF-R). These results show that the CD34(+)c-kit(+) population from the AGM represents a highly enriched source of multipotent hematopoietic cells, and suggest that limited coactivation of distinct lineage-affiliated genes is an early event in the generation of hematopoietic stem and progenitor cells during ontogeny.
Delassus
S
S
Section of Gene Function and Regulation and the Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, UK.
Titley
I
I
Enver
T
T
D000818:Animals; D018952:Antigens, CD34; D001011:Aorta / Q000166:cytology / Q000196:embryology / Q000502:physiology; D002454:Cell Differentiation; D004920:Erythropoiesis / Q000235:genetics; D005333:Fetus / Q000166:cytology* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000166:cytology / Q000196:embryology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D019891:Leukopoiesis / Q000235:genetics; D008650:Mesonephros / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit
D018952:Antigens, CD34; D019009:Proto-Oncogene Proteins c-kit