Reprogramming of Cancer Cells into Induced Pluripotent Stem Cells Questioned

Bang, Jin Seok; Choi, Na Young; Lee, Minseong; Ko, Kisung; Park, Yo Seph; Ko, Kinarm

doi:10.15283/ijsc19067

Cited by 14 publications

(20 citation statements)

References 37 publications

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“…Since the discovery that somatic cells (murine fibroblasts) could be reprogrammed into induced pluripotent stem cells (iPSCs) in 2006, an increasing number of studies have explored a more appropriate reprogramming induction system and target cells to increase reprogramming efficiency. To date, a variety of cell types have been reported to be suitable for reprogramming, including blood cells (Chen et al, 2019), adult stem cells (Jiang et al, 2019) and even cancer cells (Bang et al, 2019). With respect to corneal stromal cells, most previous studies used reprogrammed corneal fibroblasts to generate iPSCs (Greene et al, 2014;Bikkuzin et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Mechanotransduction Regulates Reprogramming Enhancement in Adherent 3D Keratocyte Cultures

Ding²,

Guo³

et al. 2021

Front. Bioeng. Biotechnol.

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Suspended spheroid culture using ultralow attachment plates (ULAPs) is reported to effect corneal fibroblast reprogramming. Polydimethylsiloxane (PDMS), with hydrophobic and soft substrate properties, facilitates adherent spheroid formation that promotes cellular physical reprogramming into stem-like cells without using transcription factors. However, it is still unknown whether the biophysical properties of PDMS have the same effect on adult human corneal keratocyte reprogramming. Here, PDMS and essential 8 (E8) medium were utilized to culture keratocyte spheroids and fibroblast spheroids, and the reprogramming results were compared. We provide insights into the probable mechanisms of the PDMS effect on spheroids. qPCR analysis showed that the expression of some stem cell marker genes (OCT4, NANOG, SOX2, KLF4, CMYC, ABCG2 and PAX6) was significantly greater in keratocyte spheroids than in fibroblast spheroids. The endogenous level of stemness transcription factors (OCT4, NANOG, SOX2, KLF4 and CMYC) was higher in keratocytes than in fibroblasts. Immunofluorescence staining revealed Klf4, Nanog, Sox2, ABCG2 and Pax6 were positively stained in adherent 3D spheroids but weakly or negatively stained in adherent 2D cells. Furthermore, OCT4, NANOG, SOX2, KLF4, HNK1, ABCG2 and PAX6 gene expression was significantly higher in adherent 3D spheroids than in adherent 2D cells. Meanwhile, SOX2, ABCG2 and PAX6 were more upregulated in adherent 3D spheroids than in suspended 3D spheroids. The RNA-seq analysis suggested that regulation of the actin cytoskeleton, TGFβ/BMP and HIF-1 signaling pathways induced changes in mechanotransduction, the mesenchymal-to-epithelial transition and hypoxia, which might be responsible for the effect of PDMS on facilitating reprogramming. In conclusion, compared to corneal fibroblasts, keratocytes were more susceptible to reprogramming due to higher levels of endogenous stemness transcription factors. Spheroid culture of keratocytes using PDMS had a positive impact on promoting the expression of some stem cell markers. PDMS, as a substrate to form spheroids, was better able to promote reprogramming than ULAPs. These results indicated that the physiological cells and culture conditions herein enhance reprogramming. Therefore, adherent spheroid culture of keratocytes using PDMS is a promising strategy to more safely promote reprogramming, suggesting its potential application for developing clinical implants in tissue engineering and regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Mechanotransduction Regulates Reprogramming Enhancement in Adherent 3D Keratocyte Cultures

Ding²,

Guo³

et al. 2021

Front. Bioeng. Biotechnol.

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“…1 ). Limited reprogramming of cancer cells displays the lower expression of pluripotency genes and increases the probability of cancer reversion [ 28 ]. Even fully reprogrammed cancer-iPSCs can reverse into originated cancer cell features over time [ 29 , 30 ].…”

Section: Cancer-ipscs and Other Pscs: A Comparison Studymentioning

confidence: 99%

Cancer cells as a new source of induced pluripotent stem cells

et al. 2022

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Over the last 2 decades, induced pluripotent stem cells (iPSCs) have had various potential applications in various medical research areas, from personalized medicine to disease treatment. Different cellular resources are accessible for iPSC generation, such as keratinocytes, skin fibroblasts, and blood or urine cells. However, all these sources are somatic cells, and we must make several changes in a somatic cell’s transcriptome and chromatin state to become a pluripotent cell. It has recently been revealed that cancer cells can be a new source of iPSCs production. Cancer cells show similarities with iPSCs in self-renewal capacity, reprogramming potency, and signaling pathways. Although genetic abnormalities and potential tumor formation in cancer cells pose a severe risk, reprogrammed cancer-induced pluripotent stem cells (cancer-iPSCs) indicate that pluripotency can transiently overcome the cancer phenotype. This review discusses whether cancer cells can be a preferable source to generate iPSCs.

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“… 1 In support of these ideas, several studies have been reported indicating that certain genes act as epigenetic barriers preventing tumor reprogramming to benign stem cell fates. 61 For instance, it has been shown that CSCs can be reprogrammed in vitro to iPSC-like states or chemically directed toward specific cell lineage commitments. 62 In another study, human pancreatic cancer cells were reprogrammed to iPSCs in vitro using episomal vectors and demonstrated a lack of tumorigenicity post-reprogramming.…”

Section: Cancer Networkmentioning

confidence: 99%

A review of dynamical systems approaches for the detection of chaotic attractors in cancer networks

Uthamacumaran

2021

Patterns

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Cancers are complex dynamical systems. They remain the leading cause of disease-related pediatric mortality in North America. To overcome this burden, we must decipher the state-space attractor dynamics of gene expression patterns and protein oscillations orchestrated by cancer stemness networks. The review provides an overview of dynamical systems theory to steer cancer research in pattern science. While most of our current tools in network medicine rely on statistical correlation methods, causality inference remains primitively developed. As such, a survey of attractor reconstruction methods and machine algorithms for the detection of causal structures applicable in experimentally derived time series cancer datasets is presented. A toolbox of complex systems approaches are discussed for reconstructing the signaling state space of cancer networks, interpreting causal relationships in their time series gene expression patterns, and assisting clinical decision making in computational oncology. As a proof of concept, the applicability of some algorithms are demonstrated on pediatric brain cancer datasets and the requirement of their time series analysis is highlighted. ll

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Reprogramming of Cancer Cells into Induced Pluripotent Stem Cells Questioned

Cited by 14 publications

References 37 publications

Mechanotransduction Regulates Reprogramming Enhancement in Adherent 3D Keratocyte Cultures

Mechanotransduction Regulates Reprogramming Enhancement in Adherent 3D Keratocyte Cultures

Cancer cells as a new source of induced pluripotent stem cells

A review of dynamical systems approaches for the detection of chaotic attractors in cancer networks

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