18 February 2019

René Dirks, with other members from the lab of Hendrik Marks, theme Cancer development and immune defense, show in a paper in Epigenetics & Chromatin that genomic imprinting (genes expressed from the paternal or maternal allele only) is often lost in cultured embryonic stem cells.

Publication in Epigenetics & Chromatin: link.

Hendrik Marks

Genomic imprinting, resulting in parent-of-origin specific gene expression, plays a critical role in mammalian development. We applied allele-specific RNA-seq to assay imprinted genes in tissues from early embryonic mouse tissues between E3.5 and E7.25 and in pluripotent cell lines to evaluate maintenance of imprinted gene expression. For the cell lines, we include embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) derived from fertilized embryos and from embryos obtained after nuclear transfer (NT) or parthenogenetic activation (PGA).

Global analysis shows that proper imprinted gene expression as observed in embryonic tissues is largely lost in the ESC lines included in this study. Differentiation of ESC lines to embryoid bodies or NPCs does not restore monoallelic expression of imprinted genes, neither did reprogramming of the serum-cultured ESCs to the pluripotent ground state by the use of 2 kinase inhibitors. Fertilized EpiSC and EpiSC-NT lines largely maintain imprinted gene expression, as did EpiSC-PGA lines that show known paternally expressed genes being silent and known maternally expressed genes consistently showing doubled expression. Notably, two EpiSC-NT lines show aberrant silencing of Rian and Meg3, two critically imprinted genes in mouse iPSCs. With respect to female EpiSC, most of the lines displayed completely skewed X inactivation suggesting a (near) clonal origin.

Our analysis provides a comprehensive overview of imprinted gene expression in pluripotency and provides a benchmark to allow identification of cell lines that faithfully maintain imprinted gene expression.and therefore retain full developmental potential.
 

Related news items


Postoperative outcome between older and younger patients with stage I-III colorectal cancer

25 June 2019

In European Journal of Cancer, Nelleke Brouwer, Thea Zonneveld-Heil and colleagues showed that differences in postoperative mortality between older and younger patients with stage I-III colorectal cancer decreased. 1-year postoperative RS was almost equal for older and younger patients in 2015-2016.

read more

Surgery to straighten a deviated septum improves quality of life

20 June 2019

Patients with a deviated septum breathe more easily after a septoplasty and their quality of life improves. Specialists have long debated its benefits. Machteld van Egmond, Maroeska Rovers, and Niels van Heerbeek have ended the controversy with a publication in The Lancet.

read more

A personal touch of Jaap ten Oever

20 June 2019

In order to promote interaction amongst colleagues within RIMLS, we have a ‘personal touch’ series setting employees in the spotlight. A light-hearted manner to learn about the colleagues you know and those you don’t. This week: Jaap ten Oever.

read more

Development of nationwide recommendations to support prenatal counseling in extreme prematurity

20 June 2019

In Pediatrics Rosa Geurtzen et al described the development of a nationwide, evidence-based framework for prenatal counseling in extreme prematurity. It contains recommendations and tools for personalization in the domains of organization, decision-making, content, and style of prenatal counseling.

read more

Remote Ischemic Conditioning as a new treatment for ischemic stroke

20 June 2019

In Stroke Thijs Landman and colleagues described the existing clinical and preclinical evidence for a new non-invasive treatment in patients with an ischemic stroke: Remote Ischemic Conditioning.

read more

Teacher of the year award for Scott Maurits

18 June 2019

On 11 June Scott Maurits received the Teacher of the Year award for a second year in a row. According to the students Scott won by being an inspirational teacher in statistics.

read more