Transcriptomic and epigenomic differences in human induced pluripotent stem cells generated from six reprogramming methods

Jared M. Churko, Jaecheol Lee, Mohamed Ameen, Mingxia Gu, Meenakshi Venkatasubramanian, Sebastian Diecke, Karim Sallam, Hogune Im, Gavin Wang, Joseph D. Gold, Nathan Salomonis, Michael P. Snyder, Joseph C. Wu

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Many reprogramming methods can generate human induced pluripotent stem cells (hiPSCs) that closely resemble human embryonic stem cells (hESCs). This has led to assessments of how similar hiPSCs are to hESCs, by evaluating differences in gene expression, epigenetic marks and differentiation potential. However, all previous studies were performed using hiPSCs acquired from different laboratories, passage numbers, culturing conditions, genetic backgrounds and reprogramming methods, all of which may contribute to the reported differences. Here, by using high-throughput sequencing under standardized cell culturing conditions and passage number, we compare the epigenetic signatures (H3K4me3, H3K27me3 and HDAC2 ChIP-seq profiles) and transcriptome differences (by RNA-seq) of hiPSCs generated from the same primary fibroblast population by using six different reprogramming methods. We found that the reprogramming method impacts the resulting transcriptome and that all hiPSC lines could terminally differentiate, regardless of the reprogramming method. Moreover, by comparing the differences between the hiPSC and hESC lines, we observed a significant proportion of differentially expressed genes that could be attributed to polycomb repressive complex targets.

Original languageEnglish (US)
Pages (from-to)826-837
Number of pages12
JournalNature Biomedical Engineering
Volume1
Issue number10
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

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  • Cite this

    Churko, J. M., Lee, J., Ameen, M., Gu, M., Venkatasubramanian, M., Diecke, S., Sallam, K., Im, H., Wang, G., Gold, J. D., Salomonis, N., Snyder, M. P., & Wu, J. C. (2017). Transcriptomic and epigenomic differences in human induced pluripotent stem cells generated from six reprogramming methods. Nature Biomedical Engineering, 1(10), 826-837. https://doi.org/10.1038/s41551-017-0141-6