Posters
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Initial studies show that forkhead box (FOXO) transcription factors support maintenance in embryonic, hematogenic, and neural stem cells. Myoblasts, embryonic precursors of myocytes, are essential for forming and maintaining skeletal muscle tissue, which can fuse to form with multinucleated myotubes. In the presence of activated PI3K-AKT pathway, FOXO factors are inactive in muscle and liver cells; however, this regulatory mechanism is bypassed in stem/stem-like cells. FOXO factors directly interact with stem-related genes like OCT4 and SOX2, facilitating their expression. Nevertheless, our understanding of the full range and conservation of FOXO transcription factor function in stem cell environments remains incomplete, leaving gaps in our knowledge. To address this, we adopted a genetic approach to uncover novel roles of FOXO factors in U87MG GBM cells, where previous research has demonstrated their ability to induce the expression of stem genes. By utilizing CRISPR Cas9 genome editing and RNA Seq analysis, we disrupted FOXO4 and identified new target genes, respectively. Our findings indicate that FOXO factors significantly enhance the expression of NOTCH1 and NOTCH3 genes in C2C12 myoblast cells. Based on this, we propose to examine whether FOXO factors redundantly contribute to the activation of the NOTCH pathway in stem or stem-like contexts such as GBM and myoblasts, influencing the fate of the cells.
Methods: To test this hypothesis, we propose to examine the ability of FOXO –1, -3, and –4 to promote the NOTCH pathway gene expression and myoblast stem cell fate. We will examine the differential expression levels of NOTCH Pathway genes and the correlation between FOXO factors and myoblast formation.
Results: The anticipated results of these procedures will be identifying NOTCH Pathway target genes regulated by FOXO transcription factors to elucidate their roles in myogenesis.
Conclusion: We conclude that delineating the roles of FOXO –1, -3, and –4 transcription factors in NOTCH Pathway regulation will help address how they drive stem cell phenotypes in myoblasts and other settings.
Academic/Professional Position
Community Partner
Recommended Citation
Barroso, Larissa; Reyes, A. M.; and Rios, S., "Investigating the Ability of FOXO Factors to Regulate the NOTCH Pathway" (2024). Research Symposium. 66.
https://scholarworks.utrgv.edu/somrs/2023/posters/66
Included in
Investigating the Ability of FOXO Factors to Regulate the NOTCH Pathway
Background: Initial studies show that forkhead box (FOXO) transcription factors support maintenance in embryonic, hematogenic, and neural stem cells. Myoblasts, embryonic precursors of myocytes, are essential for forming and maintaining skeletal muscle tissue, which can fuse to form with multinucleated myotubes. In the presence of activated PI3K-AKT pathway, FOXO factors are inactive in muscle and liver cells; however, this regulatory mechanism is bypassed in stem/stem-like cells. FOXO factors directly interact with stem-related genes like OCT4 and SOX2, facilitating their expression. Nevertheless, our understanding of the full range and conservation of FOXO transcription factor function in stem cell environments remains incomplete, leaving gaps in our knowledge. To address this, we adopted a genetic approach to uncover novel roles of FOXO factors in U87MG GBM cells, where previous research has demonstrated their ability to induce the expression of stem genes. By utilizing CRISPR Cas9 genome editing and RNA Seq analysis, we disrupted FOXO4 and identified new target genes, respectively. Our findings indicate that FOXO factors significantly enhance the expression of NOTCH1 and NOTCH3 genes in C2C12 myoblast cells. Based on this, we propose to examine whether FOXO factors redundantly contribute to the activation of the NOTCH pathway in stem or stem-like contexts such as GBM and myoblasts, influencing the fate of the cells.
Methods: To test this hypothesis, we propose to examine the ability of FOXO –1, -3, and –4 to promote the NOTCH pathway gene expression and myoblast stem cell fate. We will examine the differential expression levels of NOTCH Pathway genes and the correlation between FOXO factors and myoblast formation.
Results: The anticipated results of these procedures will be identifying NOTCH Pathway target genes regulated by FOXO transcription factors to elucidate their roles in myogenesis.
Conclusion: We conclude that delineating the roles of FOXO –1, -3, and –4 transcription factors in NOTCH Pathway regulation will help address how they drive stem cell phenotypes in myoblasts and other settings.