PDGF mediates derivation of human embryonic germ cells.
Human embryonic germ cells (hEGCs) are a valuable and underutilized source of pluripotent stem cells. Unlike embryonic stem cells, which have been extensively studied, little is known about the factors that regulate hEGC derivation and maintenance. This study demonstrates for the first time a central role for selective activation of PDGFR signaling in the derivation and maintenance of pluripotency in hEGCs. In the study, hEGCs were found to express PDGF receptor α at high levels compared to human embryonic stem cells (hESCs). PDGF significantly improved formation of alkaline phosphatase (AP) positive hEGC colonies. We subsequently determined that PDGF activates the phosphatidylinositol-3-kinase (PI3K) pathway as phosphorylation of AKT was up-regulated in response to PDGF. Furthermore, inhibition of PI3K signaling using small molecular inhibitor LY294002 led to significantly decreased AP positive hEGC colony formation whereas inhibition of MAPK pathway using U0126 had a negligible effect. We established a primary mechanism for PDGF mediated derivation and maintenance of hEGCs by demonstrating that OCT4 was upregulated and PTEN was suppressed in a dose dependent manner in response to PDGF.
Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
Yang
Y
Li
Departments of Radiology and Surgery, Stanford School of Medicine, Stanford 94305, CA, USA.
Wan Xing
WX
Hong
Fujian College of Health Occupation and Technology, Fuzhou 350001, China.
Baojin
B
Lan
Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
Xiaoyan
X
Xu
Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Yinan
Y
Liu
Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
Lin
L
Kong
Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
Yaxuan
Y
Li
Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Shixin
S
Zhou
Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Beijing 100026, China.
Ying
Y
Liu
Baotou Medical College, Baotou 014060, China.
Ruopeng
R
Feng
Department of Cell Biology and Stem Cell Research Center, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Sibo
S
Jiang
Medical and Health Analysis Center, Peking University, Beijing 100191, China.
Qihua
Q
He
Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China. Electronic address: tjczjh@163.com.
Jichun
J
Tan
D000469:Alkaline Phosphatase / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D019869:Phosphatidylinositol 3-Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases; D000469:Alkaline Phosphatase
Derivation; Human embryonic germ cells; PDGF