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Background: Pluripotency and differentiation are crucial cellular states for normal development and disease control. They are regulated by intrinsic and extrinsic factors. Master transcription factors, such as Nanog, Sox2, and Oct4, play a critical role in pluripotency, but their function in differentiation is not entirely clear. This study aims to investigate Nanog's role in differentiation using mouse embryonic stem cells as a model.
Methods: An integrative analysis was carried out using gene expression and chromatin immunoprecipitation sequencing data to determine the impact of Nanog binding on downstream gene expression. Target genes were identified as those whose expression was altered by Nanog binding, and a GSEA analysis was performed to identify shared biological processes. Additionally, Homer was utilized to conduct motif enrichment analysis at each time point.
Results: Within 24 hours of retinoic acid treatment, Nanog is recruited to newly identified sites. These sites are primarily located in intergenic regions and the genes associated with them are mainly involved in development and differentiation, specifically mesodermal and mesenchymal development. Furthermore, these recently identified sites possess enriched motifs, such as LHX1 and FLI1, which play a significant role in mesodermal differentiation, in addition to the known pluripotent and developmental transcription factors.
Conclusion: This study provides insight into the complex regulation of pluripotency and differentiation and highlights the potential role of Nanog in regulating mesodermal differentiation. It also suggests that Nanog may prefer mesodermal differentiation through indirect recruitment by factors involved in mesodermal transcription factors. Further research is needed to understand the exact mechanism of Nanog's involvement in differentiation.
Grand Forks, ND
Biochemistry, Biophysics, and Structural Biology
Aminu, Oluwatobiloba; Hur, Junguk; and de Kumar, Bony, "Understanding Nanog’s role in cell differentiation" (2023). Graduate Research Achievement Day Posters. 2.
Awarded for quality in the "Natural Sciences" category at the 2023 UND Graduate Research Achievement Day.