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Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression Signature


For those studying the effect of genotype on human traits, a collection of genetically diverse renewable cell lines can be an indispensable resource. B-cells immortalized with Epstein-Barr virus, also known as lymphoblastoid cell lines or LCLs, have been particularly favored as such a model because they are easy to generate from donor blood samples and already exist in large panels representing many ethnic and disease populations. However, long-term maintenance of LCL cultures involves practices that reduce the ability of the model to reproduce donor differences in gene expression, potentially compromising the genotype-phenotype relationship. Induced pluripotent stem cells (iPSCs) are increasingly used to study the physiology of primary tissue, and unlike LCLs, have been found to retain a strong donor effect. Recent advances have made it possible to generate iPSCs from LCLs using reprogramming vectors that do not integrate into the genome. Here, we report that reprogramming highly manipulated LCLs to iPSCs can recover donor gene expression signatures that had been lost during long-term LCL maintenance. Our findings suggest that iPSCs generated from LCL panels are well suited for studies of the genetic basis for individual phenotypic variation.


Vyšlo v časopise: Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression Signature. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005216
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005216

Souhrn

For those studying the effect of genotype on human traits, a collection of genetically diverse renewable cell lines can be an indispensable resource. B-cells immortalized with Epstein-Barr virus, also known as lymphoblastoid cell lines or LCLs, have been particularly favored as such a model because they are easy to generate from donor blood samples and already exist in large panels representing many ethnic and disease populations. However, long-term maintenance of LCL cultures involves practices that reduce the ability of the model to reproduce donor differences in gene expression, potentially compromising the genotype-phenotype relationship. Induced pluripotent stem cells (iPSCs) are increasingly used to study the physiology of primary tissue, and unlike LCLs, have been found to retain a strong donor effect. Recent advances have made it possible to generate iPSCs from LCLs using reprogramming vectors that do not integrate into the genome. Here, we report that reprogramming highly manipulated LCLs to iPSCs can recover donor gene expression signatures that had been lost during long-term LCL maintenance. Our findings suggest that iPSCs generated from LCL panels are well suited for studies of the genetic basis for individual phenotypic variation.


Zdroje

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Genetika Reprodukčná medicína

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