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Methylation profile of induced pluripotent stem cells generated by integration and integration-free approaches.

ABSTRACT: The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1]. iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, retroviruses) or by non-integrative methods (e.g., plasmids, Sendai virus, synthetic mRNAs and recombinant proteins). To evaluate the contribution of the reprogramming process isogenic system should be utilized (Shutova et al., 2016) [2]. Isogenic iPSC lines, obtained in different ways can serve the ideal system to investigate DNA methylation changes. The data presented in this article report methylation profiles for iPSC lines derived from fibroblasts of a healthy donor and PARK8-associated Parkinson's disease patient via integrating (lentiviral transfection) and non-integrating (Sendai virus infection) reprogramming using an Illumina 450K Methylation BeadChip platform. The data on DNA methylation of neurons differentiated from iPSC lines are also provided here.

SUBMITTER: Sultanov R

PROVIDER: S-EPMC5852269 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Methylation profile of induced pluripotent stem cells generated by integration and integration-free approaches.

Sultanov Rinat R Lebedeva Olga O Arapidi Georgij G Lagarkova Maria M Kiselev Sergei S

Data in brief 20180131

The genetic reprogramming technology allows generation of induced pluripotent stem cells (iPSCs) from somatic cells (Takahashi and Yamanaka, 2006) [1]. iPSCs have the ability to self-renew, and to differentiate into any type of somatic cells, and are considered as a promising tool for drug development, disease modeling, and regenerative medicine. The reprogramming factors (oct4, sox2, klf4, c-myc) can be delivered to the cell nucleus either by vectors integrating into the genome (lentiviruses, r ...[more]

PMID: 29552616

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Project description:BackgroundParental imprinting is an epigenetic mechanism that leads to monoallelic expression of a subset of genes depending on their parental origin. Imprinting disorders (IDs), caused by disturbances of imprinted genes, are a set of rare congenital diseases that mainly affect growth, metabolism and development. To date, there is no accurate model to study the physiopathology of IDs or test therapeutic strategies. Human induced pluripotent stem cells (iPSCs) are a promising cellular approach to model human diseases and complex genetic disorders. However, aberrant hypermethylation of imprinting control regions (ICRs) may appear during the reprogramming process and subsequent culture of iPSCs. Therefore, we tested various conditions of reprogramming and culture of iPSCs and performed an extensive analysis of methylation marks at the ICRs to develop a cellular model that can be used to study IDs.ResultsWe assessed the methylation levels at seven imprinted loci in iPSCs before differentiation, at various passages of cell culture, and during chondrogenic differentiation. Abnormal methylation levels were found, with hypermethylation at 11p15 H19/IGF2:IG-DMR and 14q32 MEG3/DLK1:IG-DMR, independently of the reprogramming method and cells of origin. Hypermethylation at these two loci led to the loss of parental imprinting (LOI), with biallelic expression of the imprinted genes IGF2 and DLK1, respectively. The epiPS™ culture medium combined with culturing of the cells under hypoxic conditions prevented hypermethylation at H19/IGF2:IG-DMR (ICR1) and MEG3/DLK1:IG-DMR, as well as at other imprinted loci, while preserving the proliferation and pluripotency qualities of these iPSCs.ConclusionsAn extensive and quantitative analysis of methylation levels of ICRs in iPSCs showed hypermethylation of certain ICRs in human iPSCs, especially paternally methylated ICRs, and subsequent LOI of certain imprinted genes. The epiPS™ culture medium and culturing of the cells under hypoxic conditions prevented hypermethylation of ICRs in iPSCs. We demonstrated that the reprogramming and culture in epiPS™ medium allow the generation of control iPSCs lines with a balanced methylation and ID patient iPSCs lines with unbalanced methylation. Human iPSCs are therefore a promising cellular model to study the physiopathology of IDs and test therapies in tissues of interest.

Dataset Information

Methylation profile of induced pluripotent stem cells generated by integration and integration-free approaches.

Publications

Methylation profile of induced pluripotent stem cells generated by integration and integration-free approaches.

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