title: Platelet endothelial cell adhesion molecule-1, stage-specific embryonic antigen-1, and Flk-1 mark distinct populations of mouse embryonic stem cells during differentiation toward hematopoietic/endothelial cells.
abstract: Vascular endothelial cells (ECs) and most hematopoietic cells express platelet endothelial cell adhesion molecule-1 (PECAM-1), which is the cell surface protein also expressed in mouse embryonic stem (ES) cells. To better understand how PECAM-1(+) ES cells differentiate into PECAM-1(+) hematopoietic cells/ECs, 3 cell surface markers, PECAM-1, stage-specific embryonic antigen-1 (SSEA-1), and Flk-1, were utilized to dissect the developmental process during ES cell differentiation in vitro. Undifferentiated ES cells expressed PECAM-1, with a majority of them coexpressing SSEA-1. During ES cell differentiation, expression of PECAM-1 decreased to give rise to PECAM-1⁻/SSEA-1(+) cells, which represented epiblast stem cells. Subsequently, Flk-1-expressing cells developed from PECAM-1⁻/SSEA-1(+) cells, becoming SSEA-1⁻/Flk-1(+) through the downregulation of SSEA-1 expression. Following this, a second wave of PECAM-1 expression, which represented the mature hematopoietic cells/ECs, developed from Flk-1(+) cells. Also, a small portion of PECAM-1(+)/SSEA-1(+) cells, which represented the residual undifferentiated ES cells, were consistently observed in long-term differentiated embryoid bodies. This work revealed a sequential change in PECAM-1, SSEA-1, and Flk-1 expression during ES cell differentiation; therefore, they could be valuable cell surface markers for isolating cells at distinct developmental stages in ES cell differentiation.
authors.affiliation: Department of Plastic and Reconstructive Surgery, National Tissue Engineering Center of China, Shanghai Jiao Tong University School of Medicine, Shanghai 9th People's Hospital, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yue
authors.forename: Qing Meng
authors.initials: QM
authors.lastname: Pi
authors.forename: Wen Jie
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Guang Dong
authors.initials: GD
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yilin
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006410:Hematopoiesis; D016256:Lewis X Antigen / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D055746:Stage-Specific Embryonic Antigens; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016256:Lewis X Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D055746:Stage-Specific Embryonic Antigens; D040301:Vascular Endothelial Growth Factor Receptor-2