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

Shiran Bar; Maya Schachter; Talia Eldar-Geva; Nissim Benvenisty

doi:10.1016/j.celrep.2017.04.020

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

Cell Rep. 2017 May 2;19(5):957-968. doi: 10.1016/j.celrep.2017.04.020.

Authors

Shiran Bar¹, Maya Schachter¹, Talia Eldar-Geva², Nissim Benvenisty³

Affiliations

¹ The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
² IVF Unit, Division of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel; The Hebrew University School of Medicine, Jerusalem, Israel.
³ The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. Electronic address: nissimb@mail.huji.ac.il.

PMID: 28467909
DOI: 10.1016/j.celrep.2017.04.020

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.

Keywords: DNA methylation; embryonic stem cells; maternal genes; monoallelic expression; parental imprinting; paternal genes; pluripotent stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
DNA Methylation
Embryonic Stem Cells / metabolism
Genome, Human*
Genomic Imprinting*
Humans
Pluripotent Stem Cells / metabolism*