Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon.
Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea.
Int J Stem Cells. 2014 Nov;7(2):108-17. doi: 10.15283/ijsc.2014.7.2.108.
Genomic imprinting is an inheritance phenomenon by which a subset of genes are expressed from one allele of two homologous chromosomes in a parent of origin-specific manner. Even though fine-tuned regulation of genomic imprinting process is essential for normal development, no other means are available to study genomic imprinting in human during embryonic development. In relation with this bottleneck, differentiation of human embryonic stem cells (hESCs) into specialized lineages may be considered as an alternative to mimic human development.
In this study, hESCs were differentiated into three lineage cell types to analyze temporal and spatial expression of imprinted genes. Of 19 imprinted genes examined, 15 imprinted genes showed similar transcriptional level among two hESC lines and two human induced pluripotent stem cell (hiPSC) lines. Expressional patterns of most imprinted genes were varied in progenitors and fully differentiated cells which were derived from hESCs. Also, no consistence was observed in the expression pattern of imprinted genes within an imprinting domain during in vitro differentiation of hESCs into three lineage cell types.
Transcriptional expression of imprinted genes is regulated in a cell type- specific manner in hESCs during in vitro differentiation.
基因组印迹是一种遗传现象,其中一对同源染色体中的一个等位基因按照亲本来源特异性的方式表达一部分基因。尽管精细调节基因组印迹过程对于正常发育至关重要,但在胚胎发育过程中,没有其他方法可用于研究人类的基因组印迹。针对这一瓶颈,人类胚胎干细胞(hESC)向特化谱系的分化可被视为模拟人类发育的一种替代方法。
在这项研究中,hESC 被分化为三种谱系细胞类型,以分析印迹基因的时空表达。在检查的 19 个印迹基因中,有 15 个印迹基因在两个 hESC 系和两个人类诱导多能干细胞(hiPSC)系中表现出相似的转录水平。大多数印迹基因的表达模式在源自 hESC 的祖细胞和完全分化的细胞中有所不同。此外,在 hESC 向三种谱系细胞类型体外分化过程中,印迹基因在印迹域内的表达模式没有一致性。
在 hESC 的体外分化过程中,印迹基因的转录表达以细胞类型特异性的方式受到调节。