scholarly journals The Pivotal Immunomodulatory and Anti-Inflammatory Effect of Histone-Lysine N-Methyltransferase in the Glioma Microenvironment: Its Biomarker and Therapy Potentials

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Seidu A. Richard ◽  
Kuugbee D. Eugene
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Posttranslational Modifications ◽  
Glioma Cells ◽  
Cell Types ◽  
Polycomb Group ◽  
Low Grade ◽  
Dynamic Component ◽  
Histone Lysine ◽  
Glioma Microenvironment

Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase that encrypts a member of the Polycomb group (PcG) family. EZH2 forms a repressive chromatin structure which eventually participates in regulating the development as well as lineage propagation of stem cells and glioma progression. Posttranslational modifications are distinct approaches for the adjusted modification of EZH2 in the development of cancer. The amino acid succession of EZH2 protein makes it appropriate for covalent modifications, like phosphorylation, acetylation, O-GlcNAcylation, methylation, ubiquitination, and sumoylation. The glioma microenvironment is a dynamic component that comprises, besides glioma cells and glioma stem cells, a complex network that comprises diverse cell types like endothelial cells, astrocytes, and microglia as well as stromal components, soluble factors, and the extracellular membrane. EZH2 is well recognized as an essential modulator of cell invasion as well as metastasis in glioma. EZH2 oversecretion was implicated in the malfunction of several fundamental signaling pathways like Wnt/β-catenin signaling, Ras and NF-κB signaling, PI3K/AKT signaling, β-adrenergic receptor signaling, and bone morphogenetic protein as well as NOTCH signaling pathways. EZH2 was more secreted in glioblastoma multiforme than in low-grade gliomas as well as extremely secreted in U251 and U87 human glioma cells. Thus, the blockade of EZH2 expression in glioma could be of therapeutic value for patients with glioma. The suppression of EZH2 gene secretion was capable of reversing temozolomide resistance in patients with glioma. EZH2 is a promising therapeutic as well as prognostic biomarker for the treatment of glioma.

scholarly journals The effects of mutant Ras proteins on the cell signalome

2020 ◽  
Vol 39 (4) ◽  
pp. 1051-1065 ◽  
Author(s):  
Tamás Takács ◽  
Gyöngyi Kudlik ◽  
Anita Kurilla ◽  
Bálint Szeder ◽  
László Buday ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Cell Types ◽  
Genetic Alterations ◽  
Signaling Networks ◽  
Specific Cell ◽  
Ras Proteins ◽  
Ras Genes

AbstractThe genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells.

scholarly journals Stem-Like Signature Predicting Disease Progression in Early Stage Bladder Cancer. The Role of E2F3 and SOX4

Biomedicines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 85 ◽  
Author(s):  
Joaquim Bellmunt
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Cancer Stem Cells ◽  
Tumor Progression ◽  
Cell Types ◽  
Invasive Bladder Cancer ◽  
Low Grade ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

The rapid development of the cancer stem cells (CSC) field, together with powerful genome-wide screening techniques, have provided the basis for the development of future alternative and reliable therapies aimed at targeting tumor-initiating cell populations. Urothelial bladder cancer stem cells (BCSCs) that were identified for the first time in 2009 are heterogenous and originate from multiple cell types; including urothelial stem cells and differentiated cell types—basal, intermediate stratum and umbrella cells Some studies hypothesize that BCSCs do not necessarily arise from normal stem cells but might derive from differentiated progenies following mutational insults and acquisition of tumorigenic properties. Conversely, there is data that normal bladder tissues can generate CSCs through mutations. Prognostic risk stratification by identification of predictive markers is of major importance in the management of urothelial cell carcinoma (UCC) patients. Several stem cell markers have been linked to recurrence or progression. The CD44v8-10 to standard CD44-ratio (total ratio of all CD44 alternative splicing isoforms) in urothelial cancer has been shown to be closely associated with tumor progression and aggressiveness. ALDH1, has also been reported to be associated with BCSCs and a worse prognosis in a large number of studies. UCC include low-grade and high-grade non-muscle invasive bladder cancer (NMIBC) and high-grade muscle invasive bladder cancer (MIBC). Important genetic defects characterize the distinct pathways in each one of the stages and probably grades. As an example, amplification of chromosome 6p22 is one of the most frequent changes seen in MIBC and might act as an early event in tumor progression. Interestingly, among NMIBC there is a much higher rate of amplification in high-grade NMIBC compared to low grade NMIBC. CDKAL1, E2F3 and SOX4 are highly expressed in patients with the chromosomal 6p22 amplification aside from other six well known genes (ID4, MBOAT1, LINC00340, PRL, and HDGFL1). Based on that, SOX4, E2F3 or 6q22.3 amplifications might represent potential targets in this tumor type. Focusing more in SOX4, it seems to exert its critical regulatory functions upstream of the Snail, Zeb, and Twist family of transcriptional inducers of EMT (epithelial–mesenchymal transition), but without directly affecting their expression as seen in several cell lines of the Cancer Cell Line Encyclopedia (CCLE) project. SOX4 gene expression correlates with advanced cancer stages and poor survival rate in bladder cancer, supporting a potential role as a regulator of the bladder CSC properties. SOX4 might serve as a biomarker of the aggressive phenotype, also underlying progression from NMIBC to MIBC. The amplicon in chromosome 6 contains SOX4 and E2F3 and is frequently found amplified in bladder cancer. These genes/amplicons might be a potential target for therapy. As an existing hypothesis is that chromatin deregulation through enhancers or super-enhancers might be the underlying mechanism responsible of this deregulation, a potential way to target these transcription factors could be through epigenetic modifiers.

scholarly journals Bioinformatics Analysis of Transcriptomic Data Reveals Refined Functional Networks for the Self-Renewal of Mouse Spermatogonial Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Min Wang ◽  
Wene Zhao ◽  
Fuqiang Wang ◽  
Xiufeng Ling ◽  
Daozhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Bioinformatics Analysis ◽  
Cell Types ◽  
Spermatogonial Stem Cells ◽  
Expression Index ◽  
Extrinsic Factors ◽  
Self Renewal ◽  
Proliferation And Differentiation ◽  
Disease Associations

Spermatogonial stem cells (SSCs) are exquisitely regulated to reach a balance between proliferation and differentiation in the niche of seminiferous epithelium. Several extrinsic factors such as GDNF are reported to switch the transition, activating various intrinsic signaling pathways. Transcriptomics analysis could provide a comprehensive landscape of gene expression and regulation. Here, we reanalyzed a previously published transcriptome of two cell types (standing for self-renewing and differentiating SSCs correspondingly). First, we proposed a new parameter, the expression index, to sort the genes considering both absolute and relative expression levels. Using a dynamic statistical model, we identified a list of 1119 candidate genes for SSC self-renewal with the best enrichment of canonical markers. Finally, based on interaction relations, we further optimized the list and constructed a refined network containing integrated information of interactions, expression alternations, biological functions, and disease associations. Further annotation of the 521 refined genes involved in the network revealed an enrichment of well-studied signaling pathways. We believe that the refined network could help us better understand the regulation of SSCs’ fates, as well as find novel regulators or targets for SSC self-renewal or preservation of male fertility.

Evaluation of differentiation quality of several differentiation inducers of bone marrow-derived mesenchymal stem cells to nerve cells by assessing expression of beta-tubulin 3 marker: a systematic review

2021 ◽  
Vol 16 ◽  
Author(s):  
Mohsen Karami Fath ◽  
Farhad Zahedi ◽  
Zahra Sadat Hashemi ◽  
Saeed Khalili
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathways ◽  
Histone Deacetylase Inhibitors ◽  
Neurological Diseases ◽  
Chemical Compounds ◽  
Cell Types ◽  
Nerve Cells ◽  
Beta Tubulin

: Neurological diseases have different etiological causes. Contemporary, developing an effective treatment for these diseases is an ongoing challenge. Cell therapy is recognized as one of the promising solutions for the treatment of these diseases. Amongst various types of stem cells, bone marrow-derived mesenchymal stem cells (BM-MSC) are known to be the most widely used stem cells. These cells are endowed with appealing properties such as the ability to differentiate into other cell types including the muscle, liver, glial, and nerve cells. In this review study, we have systematically evaluated the ability of a variety of chemical compounds used in the last ten years to differentiate BM-MSCs into neurons by examining the expression level of beta-tubulin 3 protein. The present study is a systematic search performed at three separate databases including PubMed, ScienceDirect, and Embase from August 2009 to August 2019. The search results in the three mentioned databases were 323 articles and finally, 8 articles were selected and carefully examined considering the inclusion and exclusion criteria. The results showed that different chemical compounds such as ROCK inhibitors, sex steroid hormones, bFGF, NGF, Noggin, 4 OHT, TSA, VPA, Antidepressants, Neurosteroids (Dex and E2), and DHA are involved in different signaling pathways such as ERK, AKT, BMP, DHA / GPR40, Rho-dependent phosphorylation, and histone deacetylase inhibitors. Further investigation of these signaling pathways may open the way for better differentiation of BM-MSCs into neurons.

scholarly journals Adrenal glands stem cells: general signaling pathways

2021 ◽  
Vol 67 (6) ◽  
pp. 90-97
Author(s):  
O. V. Glazova ◽  
M. V. Vorontsova ◽  
L. V. Shevkova ◽  
N. Sakr ◽  
N. A. Onyanov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adrenal Gland ◽  
Signaling Pathways ◽  
Cell Types ◽  
Patient Specific ◽  
Therapeutic Approaches ◽  
Adult Type ◽  
New Therapeutic Approaches ◽  
Induced Pluripotent

 Nowadays stem cells of adult type are attractive in case of active development of cell and genome technologies. They are the target of new therapeutic approaches, which are based on correction of mutations or replenishment of organs, that were damaged by autoimmune reactions, aging or other pathological processes. Also stem cells, including patient-specific (induced Pluripotent Stem Cells, iPSCs), and obtained by differentiation from them tissue cultures and organoids are the closest models to in vivo researches on humans, which gives an opportunity to get more relevant data while testing different therapeutic approaches and pharmacological drugs. The main molecular pathways, that are essential for homeostasis of a cortex of a adrenal gland — compound, structurally and functionally heterogeneous organ, is described the presented review. The adrenal cortex is renewing during the organism’s ontogenesis at the expense of the pool of stem and progenitors cells, which are in tight junctions with differentiated steroidogenic cells and which are under constant control of endocrine and paracrine signals. The understanding of signaling pathways and interactions of different cell types will give an opportunity to develop the most suitable protocols for obtaining cells of adrenal gland cortex in a different stages of differentiation to use them in scientific and medical purposes. 

scholarly journals Dppa2/4 promotes zygotic genome activation by binding to GC-rich region in signaling pathways

2020 ◽  
Author(s):  
Hanshuang Li ◽  
Chunshen Long ◽  
Jinzhu Xiang ◽  
Pengfei Liang ◽  
Yongchun Zuo
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Embryonic Stem ◽  
Cell Types ◽  
Proximal Promoter ◽  
Human Embryos ◽  
Rich Region ◽  
Cell Stage ◽  
Potent Effect ◽  
Induced Pluripotent

AbstractDevelopmental pluripotency associated 2 (Dppa2) and Dppa4 as positive drivers were helpful for transcriptional regulation of ZGA. Here, we systematically assessed the cooperative interplay between Dppa2 and Dppa4 in regulating cell pluripotency of three cell types and found that simultaneous overexpression of Dppa2/4 can make induced pluripotent stem cells closer to embryonic stem cells. Compared with other pluripotency transcription factors (TFs), Dppa2/4 tends to bind on GC-rich region of proximal promoter (0-500bp). Moreover, there was more potent effect of Dppa2/4 regulation on signaling pathways than other TFs, in which 75% and 85% signaling pathways were significantly activated by Dppa2 and Dppa4, respectively. Notably, Dppa2/4 also can dramatically trigger the decisive signaling pathways for facilitating ZGA, including Hippo, MAPK and TGF-beta signaling pathways and so on. At last, we found that Alkaline phosphatase placental-like 2 (Alppl2) was significantly activated at the 2-cell stage in mouse embryos and 4-8 cell stage in human embryos, further predicted that Alppl2 was directly regulated by Dppa2/4 as a candidate driver of ZGA to regulate pre-embryonic development.

scholarly journals Polycomb Repressive Complex(es) and Their Role in Adult Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1485
Author(s):  
Pooja Flora ◽  
Gil Dalal ◽  
Idan Cohen ◽  
Elena Ezhkova
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Adult Stem Cell ◽  
Cell Types ◽  
Polycomb Group ◽  
Polycomb Repressive Complex ◽  
Cell Compartments ◽  
Adult Tissues ◽  
Resident Stem Cells ◽  
And Function

Populations of resident stem cells (SCs) are responsible for maintaining, repairing, and regenerating adult tissues. In addition to having the capacity to generate all the differentiated cell types of the tissue, adult SCs undergo long periods of quiescence within the niche to maintain themselves. The process of SC renewal and differentiation is tightly regulated for proper tissue regeneration throughout an organisms’ lifetime. Epigenetic regulators, such as the polycomb group (PcG) of proteins have been implicated in modulating gene expression in adult SCs to maintain homeostatic and regenerative balances in adult tissues. In this review, we summarize the recent findings that elucidate the composition and function of the polycomb repressive complex machinery and highlight their role in diverse adult stem cell compartments.

scholarly journals The shift in the balance between osteoblastogenesis and adipogenesis of mesenchymal stem cells mediated by glucocorticoid receptor

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Lizhi Han ◽  
Bo Wang ◽  
Ruoyu Wang ◽  
Song Gong ◽  
Guo Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factors ◽  
Regenerative Medicine ◽  
Glucocorticoid Receptor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Efficient Treatment ◽  
Multipotent Cells

AbstractMesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into several tissues, such as bone, cartilage, and fat. Glucocorticoids affect a variety of biological processes such as proliferation, differentiation, and apoptosis of various cell types, including osteoblasts, adipocytes, or chondrocytes. Glucocorticoids exert their function by binding to the glucocorticoid receptor (GR). Physiological concentrations of glucocorticoids stimulate osteoblast proliferation and promote osteogenic differentiation of MSCs. However, pharmacological concentrations of glucocorticoids can not only induce apoptosis of osteoblasts and osteocytes but can also reduce proliferation and inhibit the differentiation of osteoprogenitor cells. Several signaling pathways, including the Wnt, TGFβ/BMP superfamily and Notch signaling pathways, transcription factors, post-transcriptional regulators, and other regulators, regulate osteoblastogenesis and adipogenesis of MSCs mediated by GR. These signaling pathways target key transcription factors, such as Runx2 and TAZ for osteogenesis and PPARγ and C/EBPs for adipogenesis. Glucocorticoid-induced osteonecrosis and osteoporosis are caused by various factors including dysfunction of bone marrow MSCs. Transplantation of MSCs is valuable in regenerative medicine for the treatment of osteonecrosis of the femoral head, osteoporosis, osteogenesis imperfecta, and other skeletal disorders. However, the mechanism of inducing MSCs to differentiate toward the osteogenic lineage is the key to an efficient treatment. Thus, a better understanding of the molecular mechanisms behind the imbalance between GR-mediated osteoblastogenesis and adipogenesis of MSCs would not only help us to identify the pathogenic causes of glucocorticoid-induced osteonecrosis and osteoporosis but also promote future clinical applications for stem cell-based tissue engineering and regenerative medicine. Here, we primarily review the signaling mechanisms involved in adipogenesis and osteogenesis mediated by GR and discuss the factors that control the adipo-osteogenic balance.

scholarly journals Dynamics of activating and repressive histone modifications in Drosophila neural stem cell lineages and brain tumors

2019 ◽  
Author(s):  
Merve Deniz Abdusselamoglu ◽  
Lisa Landskron ◽  
Sarah K. Bowman ◽  
Elif Eroglu ◽  
Thomas Burkard ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Histone Modifications ◽  
Cell Types ◽  
Polycomb Group ◽  
Epigenetic Landscape ◽  
Cell Lineages

AbstractDuring central nervous system (CNS) development, spatiotemporal gene expression programs mediate specific lineage decisions to generate neuronal and glial cell types from neural stem cells (NSCs). However, little is known about the epigenetic landscape underlying these highly complex developmental events. Here, we perform ChIP-seq on distinct subtypes of Drosophila FACS-purified neural stem cells (NSCs) and their differentiated progeny to dissect the epigenetic changes accompanying the major lineage decisions in vivo. By analyzing active and repressive histone modifications, we show that stem cell identity genes are silenced during differentiation by loss of their activating marks and not via repressive histone modifications. Our analysis also uncovers a new set of genes specifically required for altering lineage patterns in type II neuroblasts, one of the two main Drosophila NSC identities. Finally, we demonstrate that this subtype specification in NBs, unlike NSC differentiation, requires Polycomb-group (PcG)-mediated repression.Summary statementDynamic epigenetic landscape of Drosophila neural stem cell lineages.

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