Distinct Imprinting Signatures and Biased Differentiation of Human Androgenetic and Parthenogenetic Embryonic Stem Cells.
Genomic imprinting is an epigenetic mechanism that results in parent-of-origin monoallelic expression of specific genes, which precludes uniparental development and underlies various diseases. Here, we explored molecular and developmental aspects of imprinting in humans by generating exclusively paternal human androgenetic embryonic stem cells (aESCs) and comparing them with exclusively maternal parthenogenetic ESCs (pESCs) and bi-parental ESCs, establishing a pluripotent cell system of distinct parental backgrounds. Analyzing the transcriptomes and methylomes of human aESCs, pESCs, and bi-parental ESCs enabled the characterization of regulatory relations at known imprinted regions and uncovered imprinted gene candidates within and outside known imprinted regions. Investigating the consequences of uniparental differentiation, we showed the known paternal-genome preference for placental contribution, revealed a similar bias toward liver differentiation, and implicated the involvement of the imprinted gene IGF2 in this process. Our results demonstrate the utility of parent-specific human ESCs for dissecting the role of imprinting in human development and disease.
['Sagi|Ido|I|', 'De Pinho|Joao C|JC|', 'Zuccaro|Michael V|MV|', 'Atzmon|Chen|C|', 'Golan-Lev|Tamar|T|', 'Yanuka|Ofra|O|', 'Prosser|Robert|R|', 'Sadowy|Alexandra|A|', 'Perez|Gloria|G|', 'Cabral|Thiago|T|', 'Glaser|Benjamin|B|', 'Tsang|Stephen H|SH|', 'Goland|Robin|R|', 'Sauer|Mark V|MV|', 'Lobo|Rogerio|R|', 'Benvenisty|Nissim|N|', 'Egli|Dieter|D|']
D002454:Cell Differentiation D002478:Cells, Cultured D019175:DNA Methylation D053595:Embryonic Stem Cells D044127:Epigenesis, Genetic D005260:Female D020869:Gene Expression Profiling D018507:Gene Expression Regulation, Developmental D018392:Genomic Imprinting D006801:Humans D007335:Insulin-Like Growth Factor II D008297:Male D010290:Parents D010312:Parthenogenesis D039904:Pluripotent Stem Cells D012727:Sex Characteristics D059467:Transcriptome
genomic imprinting IGF2 androgenesis differentiation bias human embryonic stem cells human pluripotent stem cells parental imprinting parthenogenesis