Regulation of hemangioblast development.
The in vitro differentiation of embryonic stem (ES) cells provides a powerful approach for studying the earliest events involved in the commitment of the hematopoietic and endothelial lineages. Using this model system, we have identified a precursor with the potential to generate both primitive and definitive hematopoietic cells as well as cells with endothelial characteristics. The developmental potential of this precursor suggests that it represents the in vitro equivalent of the hemangioblast, a common stem cell for both lineages. ES cells deficient for the transcription factor scl/tal-1 are unable to generate hemangioblasts, while those deficient for Runx1 generate reduced numbers of these precursors. These findings indicate that both genes play pivotal roles at the earliest stages of hematopoietic and endothelial development. In addition, they highlight the strength of this model system in studying the function of genes in embryonic development.
Lacaud
G
G
Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, Box 1496, 1425 Madison Avenue, New York, New York 10029-6514, USA.
Robertson
S
S
Palis
J
J
Kennedy
M
M
Keller
G
G
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D005314:Embryonic and Fetal Development; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D005865:Gestational Age; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006413:Hematopoietic System / Q000196:embryology* / Q000254:growth & development; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011518:Proto-Oncogene Proteins; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015017:Yolk Sac / Q000166:cytology
D051792:Basic Helix-Loop-Helix Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human