Abstract
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.
Highlights
Primordial germ cells (PGCs) are unipotent progenitors of sperm and egg which retain an innate ability to generate pluripotent stem cells in vivo, called embryonal carcinomas (ECCs), and in vitro, known as embryonic germ cells (EGCs)
This was supported by GO analysis which demonstrated a substantial amount of energy exerted in cell cycle and metabolic processes in the stem cell lines compared to PGCs and by elevated utilization of these processes in the embryonic stem cells (ESCs), induced pluripotent stem cells (IPSCs), and ECCs compared to EGCs
We show for the first time considerably lower expression of this gene in human PGCs and EGCs compared to levels detected in ESCs, IPSCs, and ECCs further suggesting that human EGCs exist in a unique pluripotent state and that reduced DNMT3B expression may be a contributing factor for the unique chromatin state of EGCs [75]
Summary
Primordial germ cells (PGCs) are unipotent progenitors of sperm and egg which retain an innate ability to generate pluripotent stem cells in vivo, called embryonal carcinomas (ECCs), and in vitro, known as embryonic germ cells (EGCs). It is unknown whether mechanisms similar to those involved in the generation of these cells are involved in maintaining the pluripotent status of other stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (IPSCs). The first genome wide assessments of human PGCs and EGCs were performed and compared with other pluripotent ESCs, IPSCs and ECCs. PGCs are unipotent in that they are lineage-restricted to become germ cells. PGCs are unipotent in that they are lineage-restricted to become germ cells They do not exhibit self-renewal and do not survive past one week under standard tissue culture conditions [1]. PGCs first appear between the third and fourth week post-fertilization in the endoderm of the dorsal wall of the yolk sac, near the allantois, proceed to migrate through the hindgut during the fourth week and dorsal mesentery in the fifth week to reach the genital ridge [2,3,4]
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