ABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0272091.].
ABSTRACT
Reprogramming human somatic cells into a pluripotent state, achieved through the activation of well-defined transcriptional factors known as OSKM factors, offers significant potential for regenerative medicine. While OSKM factors are a robust reprogramming method, efficiency remains a challenge, with only a fraction of cells undergoing successful reprogramming. To address this, we explored genes related to genomic integrity and cellular survival, focusing on iPSCs (A53T-PD1) that displayed enhanced colony stability. Our investigation had revealed three candidate genes CCN3, POSTN, and PTHLH that exhibited differential expression levels and potential roles in iPSC stability. Subsequent analyses identified various protein interactions for these candidate genes. POSTN, significantly upregulated in A53T-PD1 iPSC line, showed interactions with extracellular matrix components and potential involvement in Wnt signaling. CCN3, also highly upregulated, demonstrated interactions with TP53, CDKN1A, and factors related to apoptosis and proliferation. PTHLH, while upregulated, exhibited interactions with CDK2 and genes involved in cell cycle regulation. RT-qPCR validation confirmed elevated CCN3 and PTHLH expression in A53T-PD1 iPSCs, aligning with RNA-seq findings. These genes' roles in preserving pluripotency and cellular stability require further exploration. In conclusion, we identified CCN3, POSTN, and PTHLH as potential contributors to genomic integrity and pluripotency maintenance in iPSCs. Their roles in DNA repair, apoptosis evasion, and signaling pathways could offer valuable insights for enhancing reprogramming efficiency and sustaining pluripotency. Further investigations are essential to unravel the mechanisms underlying their actions.
ABSTRACT
In recent years, extensive research efforts have been directed toward pluripotent stem cells, primarily due to their remarkable capacity for pluripotency. This unique attribute empowers these cells to undergo self-renewal and differentiate into various cell types originating from the ectoderm, mesoderm, and endoderm germ layers. The delicate balance and precise regulation of self-renewal and differentiation are essential for the survival and functionality of these cells. Notably, exposure to specific environmental stressors can activate numerous transcription factors, initiating a diverse array of stress response pathways. These pathways play pivotal roles in regulating gene expression and protein synthesis, ultimately aiming to preserve cell survival and maintain cellular functions. Reactive oxygen species, heat shock, hypoxia, osmotic stress, DNA damage, endoplasmic reticulum stress, and mechanical stress are among the examples of such stressors. In this review, we comprehensively discuss the impact of environmental stressors on the growth of embryonic cells. Furthermore, we provide a summary of the distinct stress response pathways triggered when pluripotent stem cells are exposed to different environmental stressors. Additionally, we highlight recent discoveries regarding the role of such stressors in the generation, differentiation, and self-renewal of induced pluripotent stem cells.
ABSTRACT
INTRODUCTION: Cystic fibrosis (CF) is a hereditary autosomal recessive disorder caused by a range of mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. This gene encodes the CFTR protein, which acts as a chloride channel activated by cyclic AMP (cAMP). This meta-analysis aimed to compare the responsiveness of induced pluripotent stem cells (iPSCs) to cAMP analogues to that of commonly used animal models. METHODS: Databases searched included PubMed, Scopus, and Medline from inception to January 2020. A total of 8 and 3 studies, respectively, for animal models and iPSCs, were analyzed. Studies were extracted for investigating cAMP-stimulated anion transport by measuring the short circuit current (Isc) of chloride channels in different animal models and iPSC systems We utilized an inverse variance heterogeneity model for synthesis. RESULTS: Our analysis showed considerable heterogeneity in the mean Isc value in both animal models and iPSCs studies (compared to their WT counterparts), and both suffer from variable responsiveness based on the nature of the underlying model. There was no clear advantage of one over the other. CONCLUSIONS: Studies on both animal and iPSCs models generated considerable heterogeneity. Given the potential of iPSC-derived models to study different diseases, we recommend paying more attention to developing reproducible models of iPSC as it has potential if adequately developed.
