Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells.
In this study, we explore endoderm cell fate regulation through the expression of lineage-determining transcription factors. We demonstrate that stable endoderm progenitors can be established from human ES cells by constitutive expression of SOX7 or SOX17, producing extraembryonic endoderm and definitive endoderm progenitors, respectively. In teratoma assays and growth factor-mediated differentiation, SOX7 cells appear restricted to the extraembryonic endoderm, and SOX17 cells demonstrate a mesendodermal phenotype in teratomas and the ability to undergo endoderm maturation in vitro in the absence of cytokine-mediated endoderm induction. These endoderm progenitor cells maintain a stable phenotype through many passages in culture, thereby providing new tools to explore the pathways of endoderm differentiation.
Séguin
Cheryle A
CA
The Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON M5G 1L7, Canada. cseguin@sickkids.ca
Draper
Jonathan S
JS
Nagy
Andras
A
Rossant
Janet
J
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013724:Teratoma / Q000235:genetics / Q000473:pathology*; D015533:Transcriptional Activation / Q000235:genetics; D014162:Transfection; D019076:Transgenes
D000943:Antigens, Differentiation; C109188:SOX17 protein, human; C484456:SOX7 protein, human; D055760:SOXF Transcription Factors