Search results for "reprogramming"

The Crosstalk Between Signaling Pathways and Cancer Metabolism in Colorectal Cancer.

2021

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Metabolic reprogramming represents an important cancer hallmark in CRC. Reprogramming core metabolic pathways in cancer cells, such as glycolysis, glutaminolysis, oxidative phosphorylation, and lipid metabolism, is essential to increase energy production and biosynthesis of precursors required to support tumor initiation and progression. Accumulating evidence demonstrates that activation of oncogenes and loss of tumor suppressor genes regulate metabolic reprogramming through the downstream signaling pathways. Protein kinases, such as AKT and c-MYC, are the integral components that facilitate the crosstalk bet…

Gene Expression and Epigenetic Signatures of Germ Cell-Derived Pluripotent Stem Cells and Embryonic Stem Cells

2012

Germ cell-derived Pluripotent Stem Cells (gPSCs) are pluripotent stem cells that originate from Spermatogonial Stem Cells (SSCs) of the testis. Several reports in the last few years have shown that it is possible to isolate and enrich the SSC population by different approaches and even reprogram these in vivo multipotent cells to gPSCs in vitro. As these cells could be an alternative to circumvent the ethical objections regarding the use of Embryonic Stem Cells (ESCs) for therapeutic approaches, these SSC-derived gPSCs were characterized in several studies comparatively to the gold standard of pluripotency, the ESCs. The results ­provide great promise that gPSCs can be of importance for pra…

PSCDGs of mouse multipotent adult germline stem cells can enter and progress through meiosis to form haploid male germ cells in vitro

2010

Spermatogonial stem cells (SSCs) provide the basis for spermatogenesis throughout adult life by undergoing self-renewal and differentiation into sperm. SSC-derived cell lines called multipotent adult germline stem cells (maGSCs) were recently shown to be pluripotent and to have the same potential as embryonic stem cells (ESCs). In a differentiation protocol using retinoic acid (RA) and based on a double selection strategy, we have shown that ESCs are able to undergo meiosis and produce haploid male germ cells in vitro. Using this differentiation protocol we have now succeeded to generate haploid male germ cells from maGSCs in vitro. maGSCs derived from a Stra8-EGFP transgenic mouse line wer…

Direct Reprogramming of Somatic Cells into Induced Neuronal Cells: Where We Are and Where We Want to Go

2014

Direct reprogramming of somatic cells has emerged as a novel strategy to generate neurons, including those of human origin. The method provides enormous potential for studying the mechanisms directing neuronal differentiation, the modeling of neurodegenerative diseases, and the development of potential novel approaches for brain repair. In this chapter, we briefly trace the history of reprogramming, as well as the strategies employed to date for converting different types of somatic cells, including fibroblasts, hepatocytes, astrocytes, and pericytes into induced neuronal cells of different subtype identity. Reprogramming involves particular emphasis on transcriptional and posttranscription…

Epigenetic regulation of stemness maintenance in the neurogenic niches

2015

In the adult mouse brain, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are two zones that contain neural stem cells (NSCs) with the capacity to give rise to neurons and glia during the entire life of the animal. Spatial and temporal regulation of gene expression in the NSCs population is established and maintained by the coordinated interaction between transcription factors and epigenetic regulators which control stem cell fate. Epigenetic mechanisms are heritable alterations in genome function that do not involve changes in DNA sequence itself but that modulate gene expression, acting as mediators between the environ…

Aberrant methylation patterns at the two-cell stage as an indicator of early developmental failure

2002

The fertilized mouse egg actively demethylates the paternal genome within a few hours after fertilization, whereas the maternal genome is only passively demethylated by a replication-dependent mechanism after the two-cell stage. This evolutionarily conserved assymetry in the early diploid mammalian embryo may have a role in methylation reprogramming of the two very different sets of sperm and egg chromatin for somatic development and formation of totipotent cells. Immunofluorescence staining with an antibody against 5-methylcytosine (MeC) showed that the incidence of abnormal methylation patterns differs between mouse two-cell embryos from superovulated females, nonsuperovulated matings, an…

Innovative Therapeutic Strategies Targeting Colorectal Cancer Stem Cells

2017

Colorectal cancer is the fourth most common cause of cancer-related death. Although many advances in the treatment of this disease have been made, a large number of patients develop metastasis and resistance to current therapies. The current evidence indicates that cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) have crucial roles in colorectal carcinogenesis and metastasis. It is also very important to understand the mechanisms that allow the survival of CSCs, such as metabolic reprogramming, which permits them to obtain specific properties or the activation of alternative signaling pathways in response to first-line therapies. In this review, we discuss the failure…

Editorial overview: Fluidity of cell fates – from reprogramming to repair

2021

Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities

2020

Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells—termed cancer stem cells (CSCs)—which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to th…

Contribution of the Cancer Stem Cell Phenotype to Hepatocellular Carcinoma Resistance

2017

The cancer stem cell (CSC) hypothesis is an increasingly accepted concept in cancer research that provides a plausible explanation for the considerable phenotypic and molecular heterogeneities observed in hepatocellular carcinoma (HCC) which hampers therapeutic progress. The hypothesis infers that CSCs share functional properties similar to adult stem cells, such as self-renewal and differentiation capacity, and are exclusively responsible for tumor evolution. By definition, CSCs are held responsible not only for tumor initiation and progression but also acquisition of chemoresistance and the fueling of relapse after therapy. Therefore, the CSC model has significant implications both for tr…