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.
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.
Yue
Wei
W
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.
Pi
Qing Meng
QM
Zhang
Wen Jie
WJ
Zhou
Guang Dong
GD
Cui
Lei
L
Liu
Wei
W
Cao
Yilin
Y
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
D016256:Lewis X Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D055746:Stage-Specific Embryonic Antigens; D040301:Vascular Endothelial Growth Factor Receptor-2