scholarly journals A Novel Regulatory Axis, CHD1L-MicroRNA 486-Matrix Metalloproteinase 2, Controls Spermatogonial Stem Cell Properties

2018 ◽  
Vol 39 (4) ◽  
Author(s):  
Shan-Shan Liu ◽  
Eithne Margaret Maguire ◽  
Yin-Shan Bai ◽  
Li Huang ◽  
Yurong Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Matrix Metalloproteinase ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Expression Profiles ◽  
Matrix Metalloproteinase 2 ◽  
Small Rna Sequencing ◽  
Growth Properties ◽  
The Matrix

ABSTRACT Spermatogonial stem cells (SSCs) are unipotent germ cells that are at the foundation of spermatogenesis and male fertility. However, the underlying molecular mechanisms governing SSC stemness and growth properties remain elusive. We have recently identified chromodomain helicase/ATPase DNA binding protein 1-like (Chd1l) as a novel regulator for SSC survival and self-renewal, but how these functions are controlled by Chd1l remains to be resolved. Here, we applied high-throughput small RNA sequencing to uncover the microRNA (miRNA) expression profiles controlled by Chd1l and showed that the expression levels of 124 miRNA transcripts were differentially regulated by Chd1l in SSCs. KEGG pathway analysis shows that the miRNAs that are differentially expressed upon Chd1l repression are significantly enriched in the pathways associated with stem cell pluripotency and proliferation. As a proof of concept, we demonstrate that one of the most highly upregulated miRNAs, miR-486, controls SSC stemness gene expression and growth properties. The matrix metalloproteinase 2 (MMP2) gene has been identified as a novel miR-486 target gene in the context of SSC stemness gene regulation and growth properties. Data from cotransfection experiments showed that Chd1l, miR-486, and MMP2 work in concert in regulating SSC stemness gene expression and growth properties. Finally, our data also revealed that MMP2 regulates SSC stemness gene expression and growth properties through activating β-catenin signaling by cleaving N-cadherin and increasing β-catenin nuclear translocation. Our data demonstrate that Chd1l–miR-486–MMP2 is a novel regulatory axis governing SSC stemness gene expression and growth properties, offering a novel therapeutic opportunity for treating male infertility.

scholarly journals Proteasomal degradation of polycomb-group protein CBX6 confers MMP-2 expression essential for mesothelioma invasion

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Katsuya Sakai ◽  
Takumi Nishiuchi ◽  
Shoichiro Tange ◽  
Yoshinori Suzuki ◽  
Seiji Yano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Mesothelioma ◽  
Molecular Mechanisms ◽  
Collagen Matrix ◽  
Proteasomal Degradation ◽  
Polycomb Group ◽  
Matrix Metalloproteinase 2 ◽  
Nuclear Staining ◽  
Polycomb Group Protein ◽  
The Matrix

Abstract The aggressive invasiveness of malignant mesothelioma limits cancer therapy, however, the molecular mechanisms underlying the invasiveness remain largely unknown. Here we found that the matrix metalloproteinase-2 (MMP-2) was required for the invasion of mesothelioma cells in the collagen matrix and the gene expression of MMP-2 was correlated with the invasive phenotype. The MMP-2 gene expression was regulated by DNA and histone methylation around the transcription start site, implicating the involvement of the polycomb repressive complex (PRC). Knockdown of PRC component chromobox 6 (CBX6) promoted MMP-2 expression and invasion of mesothelioma cells. Transcriptome analysis suggested that CBX6 regulates sets of genes involved in cancer cell migration and metastasis. In invasive but not non-invasive cells, CBX6 was constantly unstable owing to ubiquitination and protein degradation. In human tissues, CBX6 localized in the nuclei of normal mesothelium and benign mesothelioma, but the nuclear staining of CBX6 was lost in malignant mesothelioma. These results suggest involvement of proteasomal degradation of CBX6 in mesothelioma progression.

Biochemical Characterization and Gene Expression Profiling of Cytarabine Treated Stromal Fibroblasts Reveal Regulatory Mechanisms Affecting Hyaluronan and Heparan Sulfate Proteoglycans.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1304-1304
Author(s):  
Sonja Zweegman ◽  
Floortje L. Kessler ◽  
Ron Kerkhoven ◽  
Mike Heimerikx ◽  
Peter C. Huijgens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Stem Cell ◽  
Heparan Sulfate ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Critical Role ◽  
Heparan Sulfate Proteoglycans ◽  
High Dose ◽  
Pronounced Increase

Abstract High dose chemotherapy and radiation, as applied in stem cell transplantation procedures, have been found to impair the hematopoiesis-supportive capacity of bone marrow stroma. However, the molecular mechanisms involved are far from elucidated yet. As bone marrow stromal glycosaminoglycans (GAGs) play an important role in various regulatory steps in hematopoiesis, we examined the effect of chemotherapy on the synthesis and composition of GAGs and gene expression profiles of the hematopoiesis supportive M210B4 fibroblastic stromal cell line. To this end GAGs were metabolically labeled with 3H-glucosamine and 35S-sulfate, and analyzed by conventional biochemical techniques. Cytarabine treatment resulted in a pronounced increase (1.6±0.3-fold increase) in hyaluronan (HA) and a reduction in the content (47±7% reduction) and in the extent of sulfation (3H-glucosamine to 35S-sulfate ratio increased from 2,1 versus 2,6) of heparan sulfate proteoglycans (HSPG). Gene expression analysis showed a corresponding increase in hyaluronan synthase 1 (Has 1) gene expression and a decrease in hyaluronidase 2 (Hyal 2) gene expression. The decrease in HSPG was found to correspond with downregulation of the Exostosin 1 (Ext 1) gene, encoding a bifunctional glycosyltransferase, required for the biosynthesis of HS. Finally, there was a trend towards decreased expression of the N-deacetylase/N-sulfotransferase-1 (Ndst1) gene, which might explain the decrease in sulfation of HSPG after cytarabine treatment, as deacetylation is required for sulfation of HSPG to occur. The functional consequence of the decrease in HSPG was investigated by Stromal Derived Factor-1α (SDF-1α) binding. SDF-1α was added to either untreated or treated M210B4 cells and allowed to bind for 90 minutes. After washing, bound SDF-1α was quantified by staining with the anti-SDF-1α antibody K15C. Cytarabine treatment resulted in a 31.1 ± 11.8% decline in K15C binding, indicating a decline in GAG-mediated binding of SDF-1α (n=6, Mann Whitney test, p<0.05). In conclusion, cytarabine treatment alters the expression of genes involved in GAG synthesis and degradation, thereby affecting the amount and structure of stromal GAGs. Accordingly, the chemokine-binding capacity of HSPG was negatively affected. In view of the critical role of SDF-1α in migration of stem cells and its presumed participation in the creation of the stem cell niche, our results suggest that chemotherapy-induced changes in stromal GAGs might affect homing and hematopoiesis. In addition, because of known functional capacities of HA, malignant hematopoiesis as well as tumor growth and invasion may be promoted.

scholarly journals Identification of molecules derived from human fibroblast feeder cells that support the proliferation of human embryonic stem cells

2011 ◽  
Vol 16 (1) ◽  
Author(s):  
Sergey Anisimov ◽  
Nicolaj Christophersen ◽  
Ana Correia ◽  
Vanessa Hall ◽  
Ingrid Sandelin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Embryonic Stem ◽  
Feeder Cells ◽  
Continuous Growth

AbstractThe majority of human embryonic stem cell lines depend on a feeder cell layer for continuous growth in vitro, so that they can remain in an undifferentiated state. Limited knowledge is available concerning the molecular mechanisms that underlie the capacity of feeder cells to support both the proliferation and pluripotency of these cells. Importantly, feeder cells generally lose their capacity to support human embryonic stem cell proliferation in vitro following long-term culture. In this study, we performed large-scale gene expression profiles of human foreskin fibroblasts during early, intermediate and late passages using a custom DNA microarray platform (NeuroStem 2.0 Chip). The microarray data was validated using RT-PCR and virtual SAGE analysis. Our comparative gene expression study identified a limited number of molecular targets potentially involved in the ability of human neonatal foreskin fibroblasts to serve as feeder cells for human embryonic stem cell cultures. Among these, the C-KIT, leptin and pigment epithelium-derived factor (PEDF) genes were the most interesting candidates.

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4210-4218 ◽  
Author(s):  
Guibin Chen ◽  
Weihua Zeng ◽  
Akira Miyazato ◽  
Eric Billings ◽  
Jaroslaw P. Maciejewski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Small Sample ◽  
Hematopoietic Progenitor Cell ◽  
Molecular Characteristics ◽  
Hematopoietic Progenitor ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Cd34 Cells

Abstract Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.

An identification of stem cell-resembling gene expression profiles in high-grade astrocytomas

2008 ◽  
Vol 47 (11) ◽  
pp. 893-903 ◽  
Author(s):  
Yang Yang ◽  
Yongming Qiu ◽  
Wenwen Ren ◽  
Jialei Gong ◽  
Fuxue Chen
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
High Grade

scholarly journals Comparative RNA-Seq Analyses of Solenopsis japonica (Hymenoptera: Formicidae) Reveal Gene in Response to Cold Stress

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1610
Author(s):  
Mohammad Vatanparast ◽  
Youngjin Park
Keyword(s):  
Gene Expression ◽  
Cold Stress ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Predatory Behavior ◽  
P Value ◽  
Molecular Response ◽  
Rna Seq ◽  
Protein Database ◽  
Brood Chamber

Solenopsis japonica, as a fire ant species, shows some predatory behavior towards earthworms and woodlice, and preys on the larvae of other ant species by tunneling into a neighboring colony’s brood chamber. This study focused on the molecular response process and gene expression profiles of S. japonica to low (9 °C)-temperature stress in comparison with normal temperature (25 °C) conditions. A total of 89,657 unigenes (the clustered non-redundant transcripts that are filtered from the longest assembled contigs) were obtained, of which 32,782 were annotated in the NR (nonredundant protein) database with gene ontology (GO) terms, gene descriptions, and metabolic pathways. The results were 81 GO subgroups and 18 EggNOG (evolutionary genealogy of genes: Non-supervised Orthologous Groups) keywords. Differentially expressed genes (DEGs) with log2fold change (FC) > 1 and log2FC < −1 with p-value ≤ 0.05 were screened for cold stress temperature. We found 215 unigenes up-regulated and 115 unigenes down-regulated. Comparing transcriptome profiles for differential gene expression resulted in various DE proteins and genes, including fatty acid synthases and lipid metabolism, which have previously been reported to be involved in cold resistance. We verified the RNA-seq data by qPCR on 20 up- and down-regulated DEGs. These findings facilitate the basis for the future understanding of the adaptation mechanisms of S. japonica and the molecular mechanisms underlying the response to low temperatures.

scholarly journals Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

2020 ◽  
Author(s):  
Zhenhua Dang ◽  
Yuanyuan Jia ◽  
Yunyun Tian ◽  
Jiabin Li ◽  
Yanan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Grazing Intensity ◽  
Glycolate Oxidase ◽  
Bisphosphate Carboxylase ◽  
Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

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