Lineage specification of Flk-1 + progenitors is associated with divergent Sox7 expression in cardiopoiesis

Embryonic stem cell differentiation recapitulates the diverse phenotypes of a developing embryo, traceable according to markers of lineage specification. At gastrulation, the vascular endothelial growth factor (VEGF) receptor, Flk-1 (KDR), identifies a mesoderm-restricted potential of embryonic stem...

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Bibliographic Details
Published in:Differentiation (London) 2009-03, Vol.77 (3), p.248-255
Main Authors: Nelson, Timothy J., Chiriac, Anca, Faustino, Randolph S., Crespo-Diaz, Ruben J., Behfar, Atta, Terzic, Andre
Format: Article
Language:English
Subjects:
Animals
Bioinformatics
Biomarker
Cardiovascular
Cell Differentiation
Cell Line
Cell Lineage
CXCR4
Embryonic Stem Cells - cytology
Gene Expression Profiling
Gene Expression Regulation, Developmental
Mice
Myocytes, Cardiac - cytology
Progenitor
Selection
Signal Transduction
SOXF Transcription Factors - classification
SOXF Transcription Factors - metabolism
Stem cells
Vascular Endothelial Growth Factor Receptor-2 - metabolism
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Summary:Embryonic stem cell differentiation recapitulates the diverse phenotypes of a developing embryo, traceable according to markers of lineage specification. At gastrulation, the vascular endothelial growth factor (VEGF) receptor, Flk-1 (KDR), identifies a mesoderm-restricted potential of embryonic stem cells. The multi-lineage propensity of Flk-1 + progenitors mandates the mapping of fate-modifying co-factors in order to stratify differentiating cytotypes and predict lineage competency. Here, Flk-1-based selection of early embryonic stem cell progeny separated a population depleted of pluripotent ( Oct4, Sox2) and endoderm ( Sox17) markers. The gene expression profile of the Flk-1 + population was notable for a significant upregulation in the vasculogenic Sox7 transcription factor, which overlapped with the emergence of primordial cardiac transcription factors GATA-4, Myocardin and Nkx2.5. Sorting the parental Flk-1 + pool with the chemokine receptor CXCR4 to enrich the cardiopoietic subpopulation uncovered divergent Sox7 expression, with a 7-fold induction in non-cardiac compared to cardiac progenitors. Bioinformatic resolution sequestered a framework of gene expression relationship between Sox transcription factor family members and the Flk-1/CXCR4 axes with significant integration of β-catenin signaling. Thus, differential Sox7 gene expression presents a novel biomarker profile, and possible regulatory switch, to distinguish cardiovascular pedigrees within Flk-1 + multi-lineage progenitors.
ISSN:0301-4681
1432-0436
DOI:10.1016/j.diff.2008.10.012