Science University Research Symposium (SURS)

Investigating Endoderm Differentiation Following MYC and EGR1 Knockdown in Pluripotent Stem Cells

Publication Date

Fall 2025

College

College of Sciences & Mathematics

Department

Biology, Department of

SURS Faculty Advisor

Erick Spears, PhD

Presentation Type

Poster Presentation

Abstract

The Wnt signaling pathway is a key regulator of development, controlling stem cell maintenance and differentiation from embryogenesis through adulthood. In the intestinal epithelium, Wnt activation stabilizes β-catenin, leading to the transcription of target genes, such as MYC, the most well-defined function of which is to promote cell growth, metabolism, and survival. Abnormal activation of the Wnt pathway and subsequent upregulation of MYC is the driving force behind most colorectal cancers. Previous studies have shown that MYC, in the absence of p53, will drive the expression of the Early Growth Response 1 (EGR1) gene, a transcription factor involved in differentiation and response to external stimuli, ultimately stimulating apoptosis. Preliminary data also indicate that EGR1 is upregulated in definitive endoderm derived from differentiation of pluripotent stem cells down the endoderm lineage. The role of EGR1 in endoderm differentiation is unclear, and the activity of the MYC-EGR1 pathway during this process has not been assessed.

To explore this relationship, induced pluripotent stem cells (iPSCs) were transduced with shRNAs to knockdown MYC or EGR1 expression and evaluated their potential for differentiation into definitive endoderm. Using the SOX17 definitive endoderm marker, we assessed the percentage of differentiated cells in the cultures transduced with the MYC and EGR1 targeted shRNAs as compared to those transduced with a nontargeting, scrambled shRNA.

While data collection is ongoing, preliminary results suggest that decreased expression of either MYC or EGR1 decreases the number of SOX17 positive cells. These data indicate a potential role for the MYC-EGR1 pathway in the endoderm differentiation lineage. Future work will focus on verifying these effects and identifying the cellular context in iPSCs that stimulate the activation of the MYC-EGR1 pathway during endoderm differentiation.

This document is currently not available here.

Share

COinS