New Cell Models Help Researchers Study Disease Development and Growth Issues in Beckwith-Wiedemann Syndrome

Published on in CHOP News

Researchers from the Beckwith-Wiedemann Syndrome (BWS) Clinic at Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania have developed the first human cell models of Beckwith-Wiedemann syndrome (BWS), an overgrowth and cancer predisposition disorder. These models obtained from patient cells will allow them to more thoroughly investigate the role of growth differences and disease development in multiple tissues seen in patients with BWS. The findings were published in the journal Epigenetics.

The new findings involve genomic imprinting, a form of gene expression in which a small number of genes are expressed from only one parent or the other. It is a normal process involved in development, fetal and post-natal growth, and metabolism, but there are genomic imprinting disorders that include epigenetic dysregulation of imprinted genes. Beckwith-Wiedemann syndrome is the most common imprinting disorder.

Cell lines with genomic imprinting differences could allow researchers to develop models that would allow them to investigate epigenetic and transcriptional mechanisms involved in BWS. However, these cells lines cannot be easily engineered. The CHOP and Penn research team wanted to see if induced pluripotent stem cells (iPSC) could serve as an appropriate alternative. iPSC can be transitioned into multiple tissue types that are not easily accessible for study from patients.

To that end, the researchers developed the first iPSC model derived from patients with BWS. The study team derived both BWS and non-BWS iPSC lines from the same patient’s fibroblasts. Using this method, they were able to determine that DNA methylation and gene expression patterns of the imprinted region in the iPSC lines reflect cells from the patient and remain stable over time. Additionally, expressional in insulin signaling, cell proliferation and cell cycle pathways were different in BWS patients compared with their controls.

This work was supported by Alex’s Lemonade Stand Foundation, the National Institutes of Health grants T32 GM07229, GM051279, and K08 CA193915, the St. Baldrick’s Foundation and the Damon Runyon Foundation.

Chang et al, “Derivation and investigation of the first human cell-based model of Beckwith-Wiedemann syndrome.” Epigenetics. Online December 10, 2020. DOI: 10.1080/15592294.2020.1861172.