A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs.
Jiho Choi,Soohyun Lee,William Mallard,Kendell Clement,Guidantonio Malagoli Tagliazucchi,Guidantonio Malagoli Tagliazucchi,Hotae Lim,In Young Choi,Francesco Ferrari,Alexander M. Tsankov,Alexander M. Tsankov,Ramona Pop,Ramona Pop,Gabsang Lee,John L. Rinn,John L. Rinn,John L. Rinn,Alexander Meissner,Alexander Meissner,Peter J. Park,Konrad Hochedlinger,Konrad Hochedlinger +21 more
Reads0
Chats0
TLDR
It is concluded that hESCs and hiPSCs are molecularly and functionally equivalent and cannot be distinguished by a consistent gene expression signature and genetic background variation is a major confounding factor for transcriptional and epigenetic comparisons of pluripotent cell lines.Abstract:
The equivalence of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) remains controversial. Here we use genetically matched hESC and hiPSC lines to assess the contribution of cellular origin (hESC vs. hiPSC), the Sendai virus (SeV) reprogramming method and genetic background to transcriptional and DNA methylation patterns while controlling for cell line clonality and sex. We find that transcriptional and epigenetic variation originating from genetic background dominates over variation due to cellular origin or SeV infection. Moreover, the 49 differentially expressed genes we detect between genetically matched hESCs and hiPSCs neither predict functional outcome nor distinguish an independently derived, larger set of unmatched hESC and hiPSC lines. We conclude that hESCs and hiPSCs are molecularly and functionally equivalent and cannot be distinguished by a consistent gene expression signature. Our data further imply that genetic background variation is a major confounding factor for transcriptional and epigenetic comparisons of pluripotent cell lines, explaining some of the previously observed differences between genetically unmatched hESCs and hiPSCs.read more
Citations
More filters
Journal ArticleDOI
A decade of transcription factor-mediated reprogramming to pluripotency
TL;DR: The mechanisms underlying transcription factor-mediated reprogramming are still poorly understood; however, several mechanistic insights have recently been obtained, making it more amenable to applications in the fields of regenerative medicine, disease modelling and drug discovery.
Journal ArticleDOI
Common genetic variation drives molecular heterogeneity in human iPSCs
Helena Kilpinen,Angela Goncalves,Andreas Leha,Vackar Afzal,Kaur Alasoo,Sofie Ashford,Sendu Bala,Dalila Bensaddek,Francesco Paolo Casale,Oliver J. Culley,Petr Danacek,Adam Faulconbridge,Peter W. Harrison,Annie Kathuria,Davis J. McCarthy,Davis J. McCarthy,Shane A. McCarthy,Ruta Meleckyte,Yasin Memari,Nathalie Moens,Filipa A.C. Soares,Alice L. Mann,Ian Streeter,Chukwuma A. Agu,Alex Alderton,Rachel Nelson,Sarah Harper,Minal Patel,A. White,Sharad R. Patel,Laura Clarke,Reena Halai,Christopher M. Kirton,Anja Kolb-Kokocinski,Philip L. Beales,Ewan Birney,Davide Danovi,Angus I. Lamond,Willem H. Ouwehand,Willem H. Ouwehand,Willem H. Ouwehand,Ludovic Vallier,Ludovic Vallier,Fiona M. Watt,Richard Durbin,Oliver Stegle,Daniel J. Gaffney +46 more
TL;DR: This study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer.
Journal ArticleDOI
Dynamic stem cell states: naive to primed pluripotency in rodents and humans
TL;DR: This Review integrates recent discoveries related to isolating unique naive and primed pluripotent stem cell states with altered functional and molecular characteristics, and from different species, to provide an overview of the pathways underlying pluripotency transitions and interconversion in vitro and in vivo.
Journal ArticleDOI
Pluripotent Stem Cell-Based Cell Therapy—Promise and Challenges
TL;DR: Two decades of research aimed at overcoming practical issues that limit ESCs and iPSCs use, including their inherent properties of tumorigenicity, immunogenicity, and heterogeneity are reviewed.
Journal ArticleDOI
DNA Damage in Stem Cells.
TL;DR: The pathophysiological and therapeutic implications of the molecular pathways through which stem cells cope with DNA damage are discussed.
References
More filters
Journal ArticleDOI
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
Journal ArticleDOI
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.
TL;DR: EdgeR as mentioned in this paper is a Bioconductor software package for examining differential expression of replicated count data, which uses an overdispersed Poisson model to account for both biological and technical variability and empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference.
Journal ArticleDOI
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
Journal ArticleDOI
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
TL;DR: Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches and can be used simultaneously to achieve even greater alignment speeds.
Journal ArticleDOI
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
Related Papers (5)
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
Epigenetic memory in induced pluripotent stem cells
Kibem Kim,Akiko Doi,Bo Wen,K. Ng,Rui Zhao,Patrick Cahan,Jonghwan Kim,Martin J. Aryee,Hong Ji,Lauren I.R. Ehrlich,Lauren I.R. Ehrlich,A. Yabuuchi,A. Takeuchi,K. C. Cunniff,H. Hongguang,Shannon McKinney-Freeman,Olaia Naveiras,T. J. Yoon,T. J. Yoon,Rafael A. Irizarry,Namyoung Jung,Jun Seita,Jacob H. Hanna,Peter Murakami,Rudolf Jaenisch,Ralph Weissleder,Stuart H. Orkin,Irving L. Weissman,Andrew P. Feinberg,George Q. Daley +29 more