Dataset Information

Assessment of genetic and epigenetic variation in human IPS cells

ABSTRACT: In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs but it is unlcear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.

PROVIDER: EGAS00001000492 | EGA |

REPOSITORIES: EGA

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Publications

Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.

Rouhani Foad J FJ Nik-Zainal Serena S Wuster Arthur A Li Yilong Y Conte Nathalie N Koike-Yusa Hiroko H Kumasaka Natsuhiko N Vallier Ludovic L Yusa Kosuke K Bradley Allan A

PLoS genetics 20160407 4

The accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. Howe ...[more]

PMID: 27054363

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Project description:The reprogramming of human fibroblasts to generate induced pluripotent stem cells (hiPSCs) has been achieved through the expression of only a few exotic factors1-8, which is morphologically and molecularly verified in outer cellular states by characteristic markers, due to the remodeling of the somatic cell transcription programs in inner cellular states to the ES-like condition. Transcription factor-induced reprogramming to self-renewal and pluripotency raises the question as to how the exotic factors act to bring about these changes in the two cellular states9-11. Here, we applied RNA profiling to uncover gene expression changes and glycan profiling12 to survey structural changes in glycans, to compare hiPSCs and parental somatic cells, in total 51 cells, which were originally cultured and established, and the changes were analyzed by the combination of standard statistical techniques and a network approach13. We fist found a gene expression signature of 2502 genes with significant difference between iPSCs and SCs, and by the following network analysis by considering the expression signature, we found a network signature of 28 regulatory networks of 76 genes, which were related to the glycan biosynthetic pathways including 3 glycosyltransferase, in addition to well known signal pathways and cell-cell interaction pathways. Concomitantly, we found a glycan signature of six glycan structures characterized 16 lectins on lectin microarray by the correspondence with 12 glycosyltransferases in expression signature. In particular, the correspondence detected between the three expression signatures revealed 14 candidate glycosyltransferase, which are responsible for glycan transfer related to known epitopes for the differentiation such as SSEA epitope family in glycan biosynthesis pathway, based on characteristic changes in the cellular surface states of the hiPSCs. This sheds new light on a possible linkage between the inner and outer cellular states for reprogramming to self-renewal and pluripotency in hiPSC. Gene expressions in human induced pluripotent stem (iPS) cells and the provenance somatic cells . iPS cells were induced from four different somatic cells by infection of the retroviral vectors pMXs encoding OCT3/4, SOX2, KLF4 and c-MYC, simultaneously.

Dataset Information

Assessment of genetic and epigenetic variation in human IPS cells

Publications

Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.

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