A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs

Choi, Jiho; Lee, Mi Kyung; Mallard, William; Clement, Kendell; Tagliazucchi, Guidantonio Malagoli; Lim, Hotae; Choi, In Young; Ferrari, Francesco; Tsankov, Alexander M.; Pop, Ramona; Lee, Gabsang; Rinn, John L.; Meissner, Alexander; Park, Peter J.; Hochedlinger, Konrad

doi:10.1038/nbt.3388

Cited by 244 publications

(255 citation statements)

References 56 publications

(63 reference statements)

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“…Differences in endogenous signalling activity may also contribute to the heterogeneity of iPSC lines generated from the same tissue sample (35). A recent study on variation between pluripotent cell lines indicates that a difference in genetic background is the major factor for variation, rather than aberrations arising during viral transfection (36). In the authors' experience, extended passaging of iPSC lines did not promote differences in hepatic differentiation, irrespective of the parental tissue of origin.…”

Section: Ips and Es Cells How Similar Are They?mentioning

confidence: 64%

Pluripotent stem cells to hepatocytes, the journey so far

2017

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Abstract. Over the past several years, there has been substantial progress in the field of regenerative medicine, which has enabled new possibilities for research and clinical application. For example, there are ongoing efforts directed at generating functional hepatocytes from adult-derived pluripotent cells for toxicity screening, generating disease models or, in the longer term, for the treatment of liver failure. In the present review, the authors summarise recent developments in regenerative medicine and pluripotent stem cells, the methods and tissues used for reprogramming and the differentiation of induced pluripotent stem cells (iPSCs) into hepatocyte-like cells. In addition, the hepatic disease models developed using iPSC technologies are discussed, as well as the potential for gene editing.

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Section: Ips and Es Cells How Similar Are They?mentioning

confidence: 64%

Pluripotent stem cells to hepatocytes, the journey so far

2017

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“…These properties make iPSCs a valuable cellular model for the study of gene regulation in a controlled setting. Although some debate remains about whether iPSCs are truly equivalent to embryonic stem cells (ESCs), studies have shown, using wellmatched lines, that iPSCs are nearly indistinguishable from ESCs in their molecular profiles and their ability to differentiate (D'Aiuto et al 2014;Pagliuca et al 2014;Choi et al 2015;Davidson et al 2015).…”

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confidence: 99%

Impact of regulatory variation across human iPSCs and differentiated cells

et al. 2017

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Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression levels, chromatin accessibility, and DNA methylation. Our analysis focused on a comparison of inter-individual regulatory variation across cell types. While most cell-type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell-type-specific regulatory QTLs are in shared open chromatin. This observation motivated us to develop a deep neural network to predict open chromatin regions from DNA sequence alone. Using this approach, we were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell-type-specific chromatin accessibility.

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“…Some of these mutations can also be resolved with longer passaging, presumably to select against them and restore a more ES-like genetic state [39]. Using genetically matched human iPS and ES cells identified only 49 differentially expressed genes which did not affect the potential of these lines, leading the authors to conclude that genetic background has a greater influence on the differences between ES and iPS cells that has been previously observed, rather than a functional difference between these two cell types [20].…”

Section: Bioinformatic Analysis Of Induced Pluripotencymentioning

confidence: 73%

Bioinformatic and Genomic Analyses of Cellular Reprogramming and Direct Lineage Conversion

Kareta

2016

Curr Pharmacol Rep

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Cellular reprogramming, whereby cell fate can be changed by the expression of a few defined factors, is a remarkable process that harnesses the innate ability of a cell's own genome to rework its expressional networks and function. Since cell lineages are defined by global regulation of gene expression, transcriptional regulators, and coupled to the epigenetic markings of the chromatin, changing the cell fate necessitates broad changes to these central cellular features. To properly characterize these changes, and the mechanisms that drive them, computational and genomic approaches are perfectly suited to provide a holistic picture of the reprogramming mechanisms. In particular, the use of bioinformatic analysis has been a major driver in the study of cellular reprogramming, as it relates to both induced pluripotency or direct lineage conversion. This review will summarize many of the bioinformatic studies that have advanced our knowledge of reprogramming and address future directions for these investigations.

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A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs

Cited by 244 publications

References 56 publications

Pluripotent stem cells to hepatocytes, the journey so far

Pluripotent stem cells to hepatocytes, the journey so far

Impact of regulatory variation across human iPSCs and differentiated cells

Bioinformatic and Genomic Analyses of Cellular Reprogramming and Direct Lineage Conversion

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