Establishment of Homozygote Mutant Human Embryonic Stem Cells by Parthenogenesis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Oct 17

PMID 26473610

Citations 3

Authors

Silvina Epsztejn-Litman

Yaara Cohen-Hadad

Shira Aharoni

Gheona Altarescu

Paul Renbaum

Ephrat Levy-Lahad

Oshrat Schonberger

Talia Eldar-Geva

Sharon Zeligson

Rachel Eiges

Affiliations

Soon will be listed here.

Abstract

We report on the derivation of a diploid 46(XX) human embryonic stem cell (HESC) line that is homozygous for the common deletion associated with Spinal muscular atrophy type 1 (SMA) from a pathenogenetic embryo. By characterizing the methylation status of three different imprinted loci (MEST, SNRPN and H19), monitoring the expression of two parentally imprinted genes (SNRPN and H19) and carrying out genome-wide SNP analysis, we provide evidence that this cell line was established from the activation of a mutant oocyte by diploidization of the entire genome. Therefore, our SMA parthenogenetic HESC (pHESC) line provides a proof-of-principle for the establishment of diseased HESC lines without the need for gene manipulation. As mutant oocytes are easily obtained and readily available during preimplantation genetic diagnosis (PGD) cycles, this approach should provide a powerful tool for disease modelling and is especially advantageous since it can be used to induce large or complex mutations in HESCs, including gross DNA alterations and chromosomal rearrangements, which are otherwise hard to achieve.

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