Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells.
Human embryonic germ cells (EGCs) provide a powerful model for identifying molecules involved in the pluripotent state when compared to their progenitors, primordial germ cells (PGCs), and other pluripotent stem cells. Microarray and Principal Component Analysis (PCA) reveals for the first time that human EGCs possess a transcription profile distinct from PGCs and other pluripotent stem cells. Validation with qRT-PCR confirms that human EGCs and PGCs express many pluripotency-associated genes but with quantifiable differences compared to pluripotent embryonic stem cells (ESCs), induced pluripotent stem cells (IPSCs), and embryonal carcinoma cells (ECCs). Analyses also identified a number of target genes that may be potentially associated with their unique pluripotent states. These include IPO7, MED7, RBM26, HSPD1, and KRAS which were upregulated in EGCs along with other pluripotent stem cells when compared to PGCs. Other potential target genes were also found which may contribute toward a primed ESC-like state. These genes were exclusively up-regulated in ESCs, IPSCs and ECCs including PARP1, CCNE1, CDK6, AURKA, MAD2L1, CCNG1, and CCNB1 which are involved in cell cycle regulation, cellular metabolism and DNA repair and replication. Gene classification analysis also confirmed that the distinguishing feature of EGCs compared to ESCs, ECCs, and IPSCs lies primarily in their genetic contribution to cellular metabolism, cell cycle, and cell adhesion. In contrast, several genes were found upregulated in PGCs which may help distinguish their unipotent state including HBA1, DMRT1, SPANXA1, and EHD2. Together, these findings provide the first glimpse into a unique genomic signature of human germ cells and pluripotent stem cells and provide genes potentially involved in defining different states of germ-line pluripotency.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Nikta
N
Pashai
Haiping
H
Hao
Angelo
A
All
Siddharth
S
Gupta
Raghothama
R
Chaerkady
Alejandro
A
De Los Angeles
John D
JD
Gearhart
Candace L
CL
Kerr
D000818:Animals; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling / Q000379:methods*; D016678:Genome; D055106:Genome-Wide Association Study; D005854:Germ Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D008858:Microscopy, Phase-Contrast / Q000379:methods; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology*; D025341:Principal Component Analysis; D014158:Transcription, Genetic