Large-Scale Analysis of Loss of Imprinting in Human Pluripotent Stem Cells

Shiran Bar, Maya Schachter, Talia Eldar-Geva, Nissim Benvenisty*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

The parent-specific monoallelic expression of imprinted genes is controlled by DNA methylation marks that are established differentially in the germline. Perturbation of these marks leads to loss of imprinting (LOI), which is associated with developmental disorders and malignancy and may also obstruct applications of human pluripotent stem cells (hPSCs). Previous studies of LOI in hPSCs were performed on relatively small numbers of cell lines, often leading to conflicting conclusions regarding imprinting stability. Here, we chart the landscape of LOI in hPSCs by applying a large-scale analysis of allele-specific RNA-seq data from more than 270 hPSC samples. We show that reprogrammed hPSCs acquire higher levels of LOI compared with embryonic stem cells and that LOI can pre-exist in their somatic cells of origin. Furthermore, different imprinted genes vary with respect to LOI incidence, surprisingly revealing that those controlled paternally are more prone to disruption. Our findings emphasize the importance of inspecting the imprinting status of hPSCs.

Original languageAmerican English
Pages (from-to)957-968
Number of pages12
JournalCell Reports
Volume19
Issue number5
DOIs
StatePublished - 2 May 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s)

Keywords

  • DNA methylation
  • embryonic stem cells
  • maternal genes
  • monoallelic expression
  • parental imprinting
  • paternal genes
  • pluripotent stem cells

Fingerprint

Dive into the research topics of 'Large-Scale Analysis of Loss of Imprinting in Human Pluripotent Stem Cells'. Together they form a unique fingerprint.

Cite this