Project description: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 new 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 novel bias towards 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.
Project description: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.
Project description: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.
Project description:Distinct imprinting signatures and biased differentiation of human androgenetic and parthenogenetic embryonic stem cells [microarray]
Project description:Distinct imprinting signatures and biased differentiation of human androgenetic and parthenogenetic embryonic stem cells [RNA-Seq II]
Project description:Distinct imprinting signatures and biased differentiation of human androgenetic and parthenogenetic embryonic stem cells [RNA-Seq I]
Project description:In this study, mRNA expression profiles were examined by Illumina microarray in mouse embryonic stem cells (ESCs) derived from androgenetic (aESC), parthenogenetic (pESC) and fertilized (fESC) blastocysts. Results showed that 2394, 87 and 1788 mRNAs were differentially expressed in the aESCs vs. fESCs, pESCs vs. fESCs and aESCs vs. pESCs, respectively. Androgenetic, parthenogenetic and fertilized embryonic stem cell lines were established from androgenetic, parthenogenetically activated and fertilized blasotocyst. mRNA microarrays were repeated three times using passages 6, 7 and 8.
Project description:Genomic imprinting is an epigenetic phenomenon in which the expression of a gene is determined in a parent-of-origin-dependent manner. Imprinted genes play an important role in the normal growth and development of mammals, and mutations at the imprinting sites result in gene dysfunction and many genetic disorders. To identify new human imprinted differentially methylated regions (DMRs), we compared the global levels of DNA methylation in androgenetic induced pluripotent stem cells and parthenogenetic induced pluripotent stem cells using DNA methyl-capture sequencing analysis.