Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells.
Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells.
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DOI：
10.1371/journal.pone.0039088
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kerr CL
中科院分区：
文献类型：
--
作者：
Pashai N;Hao H;All A;Gupta S;Chaerkady R;De Los Angeles A;Gearhart JD;Kerr CL
人胚胎生殖细胞（EGCs）提供了一个强大的模型，用于识别分子参与多能状态相比，其祖细胞，原始生殖细胞（PGCs），和其他多能干细胞。微阵列和主成分分析（PCA）首次揭示了人类EGCs具有不同于PGCs和其他多能干细胞的转录谱。用qRT-PCR验证证实，人EGC和PGC表达许多多能性相关基因，但与多能性胚胎干细胞（ESC）、诱导多能性干细胞（IPSC）和胚胎癌细胞（ECC）相比具有可量化的差异。分析还确定了一些可能与其独特的多能状态潜在相关的靶基因。这些包括IPO 7、MED 7、RBM 26、HSPD 1和KRAS，当与PGCs相比时，它们在EGCs中与其他多能干细胞沿着上调。其他潜在的靶基因也被发现，这可能有助于启动ESC样状态。这些基因仅在ESC、IPSC和ECCs中上调，包括PARP 1、CCNE 1、CDK 6、AURKA、MAD 2L 1、CCNG 1和CCNB 1，它们参与细胞周期调节、细胞代谢和DNA修复和复制。基因分类分析也证实了EGCs与ESC、ECCs和IPSC相比的区别特征主要在于它们对细胞代谢、细胞周期和细胞粘附的遗传贡献。相比之下，发现几个基因在PGCs中上调，这可能有助于区分它们的单能状态，包括HBA 1，DMRT 1，SPAN XA 1和EHD 2。总之，这些发现提供了对人类生殖细胞和多能干细胞独特基因组特征的第一次一瞥，并提供了可能参与定义生殖系多能性不同状态的基因。
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.
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