Lineage analysis of the hemangioblast as defined by FLK1 and SCL expression.
Accumulating studies support the idea that a common progenitor, termed the hemangioblast, generates both hematopoietic and endothelial cell lineages. To better define the relationship between these cell lineages, we have generated knock-in embryonic stem (ES) cells carrying a non-functional human CD4 at the Scl locus. By using in vitro differentiated Scl(+/CD4) ES cells, we demonstrate that FLK1 and SCL are molecular determinants of the hemangioblast. Furthermore, our studies demonstrate that hematopoietic and endothelial cells develop via distinct, sequential generation of FLK1 and SCL-expressing cells. FLK1(+)CD4(-) cells first arise in developing embryoid bodies. The Scl gene is turned on within FLK1(+)CD4(-) cells to give rise to FLK1(+)CD4(+) cells. Alternatively, a subpopulation of the initial FLK1(+)CD4(-) cells remains as SCL negative. Within the FLK1(+)CD4(+) cells, FLK1 is down regulated to generate FILK1(-)CD4(+) cells. Replating studies demonstrate that hematopoietic progenitors are enriched within FLK1(+)CD4(+) and FLK1(-)CD4(+) cells, while endothelial cells develop from FLK1(+)CD4(+) and FLK1(+)CD4(-) cell populations.
Chung
Yun Shin
YS
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Zhang
Wen Jie
WJ
Arentson
Elizabeth
E
Kingsley
Paul D
PD
Palis
James
J
Choi
Kyunghee
K
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015704:CD4 Antigens / Q000235:genetics; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004727:Endothelium / Q000254:growth & development* / Q000502:physiology; D005434:Flow Cytometry; D018390:Gene Targeting; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D040301:Vascular Endothelial Growth Factor Receptor-2; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human