scholarly journals Expression Profile of PIN-Formed Auxin Efflux Carrier Genes during IBA-Induced In Vitro Adventitious Rooting in Olea europaea L.

Plants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 185 ◽  
Author(s):  
Isabel Velada ◽  
Hélia Cardoso ◽  
Sara Porfirio ◽  
Augusto Peixe
Keyword(s):  
Gene Expression ◽  
Plant Species ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Economic Value ◽  
Adventitious Rooting ◽  
Olive Cultivar ◽  
Olive Cultivars ◽  
Auxin Redistribution

Exogenous auxins supplementation plays a central role in the formation of adventitious roots (AR) for several plant species. However, the molecular mechanisms underlying the process of adventitious rooting are still not completely understood and many plants with economic value, including several olive cultivars, exhibit a recalcitrant behavior towards cutting propagation, which limits its availability in plant nurseries. PIN-formed proteins are auxin efflux transporters that have been widely characterized in several plant species due to their involvement in many developmental processes including root formation. The present study profiled the expression of the OePIN1a-c, OePIN2b, OePIN3a-c, OePIN5a-c, OePIN6, and OePIN8 gene members during indole-3-butyric acid (IBA)-induced in vitro adventitious rooting using the olive cultivar ‘Galega vulgar’. Gene expression analysis by quantitative real time PCR (RT-qPCR) showed drastic downregulation of most transcripts, just a few hours after explant inoculation, in both nontreated and IBA-treated microcuttings, albeit gene downregulation was less pronounced in IBA-treated stems. In contrast, OePIN2b showed a distinct expression pattern being upregulated in both conditions, and OePIN5b was highly upregulated in IBA-induced stems. All transcripts, except OePIN8, showed different expression profiles between nontreated and IBA-treated explants throughout the rooting experiment. Additionally, high levels of reactive oxygen species (ROS) were observed soon after explant preparation, decreasing a few hours after inoculation. Altogether, the results suggest that wounding-related ROS production, associated with explant preparation for rooting, may have an impact on auxin transport and distribution via changes in OePIN gene expression. Moreover, the application of exogenous auxin may modulate auxin homeostasis through regulation of those genes, leading to auxin redistribution throughout the stem-base tissue, which may ultimately play an important role in AR formation.

scholarly journals Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Masahiro Asakawa ◽  
Michiko Itoh ◽  
Takayoshi Suganami ◽  
Takeru Sakai ◽  
Sayaka Kanai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Xenograft Model ◽  
Gene Expression Profiles ◽  
Sequencing Analysis ◽  
Alcoholic Steatohepatitis ◽  
Activated Fibroblasts

AbstractNon-alcoholic steatohepatitis (NASH), characterized by chronic inflammation and fibrosis, is predicted to be the leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the next decade. Although recent evidence suggests the importance of fibrosis as the strongest determinant of HCC development, the molecular mechanisms underlying NASH-induced carcinogenesis still remain unclear. Here we performed RNA sequencing analysis to compare gene expression profiles of activated fibroblasts prepared from two distinct liver fibrosis models: carbon tetrachloride–induced fibrosis as a model without obesity and HCC and genetically obese melanocortin 4 receptor–deficient (MC4R-KO) mice fed Western diet, which develop steatosis, NASH, and eventually HCC. Our data showed that activated fibroblasts exhibited distinct gene expression patterns in each etiology, and that the ‘pathways in cancer’ were selectively upregulated in the activated fibroblasts from MC4R-KO mice. The most upregulated gene in these pathways was fibroblast growth factor 9 (FGF9), which was induced by metabolic stress such as palmitate. FGF9 exerted anti-apoptotic and pro-migratory effects in fibroblasts and hepatoma cells in vitro and accelerated tumor growth in a subcutaneous xenograft model. This study reveals upregulation of cancer-associated gene expression in activated fibroblasts in NASH, which would contribute to the progression from NASH to HCC.

scholarly journals Molecular signature of anastasis for reversal of apoptosis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 43 ◽  
Author(s):  
Ho Man Tang ◽  
C. Conover Talbot Jr ◽  
Ming Chiu Fung ◽  
Ho Lam Tang
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Cancer Cell Line ◽  
Molecular Signature ◽  
Cell Recovery ◽  
Therapeutic Implications

Anastasis (Greek for "rising to life") is a cell recovery phenomenon that rescues dying cells from the brink of cell death. We recently discovered anastasis to occur after the execution-stage of apoptosis in vitro and in vivo. Promoting anastasis could in principle preserve injured cells that are difficult to replace, such as cardiomyocytes and neurons. Conversely, arresting anastasis in dying cancer cells after cancer therapies could improve treatment efficacy. To develop new therapies that promote or inhibit anastasis, it is essential to identify the key regulators and mediators of anastasis – the therapeutic targets. Therefore, we performed time-course microarray analysis to explore the molecular mechanisms of anastasis during reversal of ethanol-induced apoptosis in mouse primary liver cells. We found striking changes in transcription of genes involved in multiple pathways, including early activation of pro-cell survival, anti-oxidation, cell cycle arrest, histone modification, DNA-damage and stress-inducible responses, and at delayed times, angiogenesis and cell migration. Validation with RT-PCR confirmed similar changes in the human liver cancer cell line, HepG2, during anastasis. Here, we present the time-course whole-genome gene expression dataset revealing gene expression profiles during the reversal of apoptosis. This dataset provides important insights into the physiological, pathological, and therapeutic implications of anastasis.

scholarly journals USP22-dependent HSP90AB1 expression promotes resistance to HSP90 inhibition in mammary and colorectal cancer

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Robyn Laura Kosinsky ◽  
Marlena Helms ◽  
Maria Zerche ◽  
Luisa Wohn ◽  
Anna Dyas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Signature ◽  
Breast Cancer Cell Lines ◽  
Mcf10a Cell ◽  
Hsp90 Inhibition

AbstractAs a member of the 11-gene “death-from-cancer” gene expression signature, overexpression of the Ubiquitin-Specific Protease 22 (USP22) was associated with poor prognosis in various human malignancies. To investigate the function of USP22 in cancer development and progression, we sought to detect common USP22-dependent molecular mechanisms in human colorectal and breast cancer cell lines. We performed mRNA-seq to compare gene expression profiles of various colorectal (SW837, SW480, HCT116) and mammary (HCC1954 and MCF10A) cell lines upon siRNA-mediated knockdown of USP22. Intriguingly, while USP22 depletion had highly heterogeneous effects across the cell lines, all cell lines displayed a common reduction in the expression of Heat Shock Protein 90 Alpha Family Class B Member 1 (HSP90AB1). The downregulation of HSP90AB1 was confirmed at the protein level in these cell lines as well as in colorectal and mammary tumors in mice with tissue-specific Usp22 deletions. Mechanistically, we detected a significant reduction of H3K9ac on the HSP90AB1 gene in USP22-deficient cells. Interestingly, USP22-deficient cells displayed a high dependence on HSP90AB1 expression and diminishing HSP90 activity further using the HSP90 inhibitor Ganetespib resulted in increased therapeutic vulnerability in both colorectal and breast cancer cells in vitro. Accordingly, subcutaneously transplanted CRC cells deficient in USP22 expression displayed increased sensitivity towards Ganetespib treatment in vivo. Together, we discovered that HSP90AB1 is USP22-dependent and that cooperative targeting of USP22 and HSP90 may provide an effective approach to the treatment of colorectal and breast cancer.

scholarly journals Activation of the Anaphase Promoting Complex reverses multiple drug resistant cancer

2020 ◽  
Author(s):  
T.G. Arnason ◽  
V. MacDonald-Dickinson ◽  
J.F. Davies ◽  
L. Lobanova ◽  
C. Gaunt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Multiple Drug Resistance ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Multiple Drug ◽  
Anaphase Promoting Complex ◽  
Insulin Sensitizer

ABSTRACTLike humans, canines spontaneously develop lymphomas that are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make them excellent models to study MDR mechanisms. We previously demonstrated that adjunct treatment of in vitro MDR cell lines with insulin-sensitizers effectively restored MDR chemosensitivity and prevented MDR development. This study extends the use of an insulin-sensitizer to clinical and tumor responses in vivo in volunteer canines with MDR lymphoma, including assessing changes in MDR protein biomarkers and global gene expression. Longitudinal tumor sampling and analysis of MDR cases throughout treatment allowed a correlation between in vivo molecular mechanisms and clinical responsiveness. We found reduced MDR biomarkers within all tumors, yet only one canine entered clinical remission. Analysis of tumor samples during remission and relapse allowed comparison of gene expression profiles. This revealed the Anaphase Promoting Complex (APC), a ubiquitin-E3 ligase regulating cell cycle progression, was impaired during chemoresistance/MDR and restored during remission. Validating in vitro tests restored MDR chemosensitivity upon APC activation, supporting the idea that APC activity is an important underlying cellular mechanism associated with treatment resistance, and a novel potential therapeutic target.

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 Molecular signature of anastasis for reversal of apoptosis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 43 ◽  
Author(s):  
Ho Man Tang ◽  
C. Conover Talbot Jr ◽  
Ming Chiu Fung ◽  
Ho Lam Tang
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Molecular Signature ◽  
Cell Recovery ◽  
Therapeutic Implications

Apoptosis is a type of programmed cell death that is essential for normal organismal development and homeostasis of multicellular organisms by eliminating unwanted, injured, or dangerous cells. This cell suicide process is generally assumed to be irreversible. However, accumulating studies suggest that dying cells can recover from the brink of cell death. We recently discovered an unexpected reversibility of the execution-stage of apoptosis in vitro and in vivo, and proposed the term anastasis (Greek for “rising to life”) to describe this cell recovery phenomenon. Promoting anastasis could in principle preserve injured cells that are difficult to replace, such as cardiomyocytes and neurons. Conversely, arresting anastasis in dying cancer cells after cancer therapies could improve treatment efficacy. To develop new therapies that promote or inhibit anastasis, it is essential to identify the key regulators and mediators of anastasis – the therapeutic targets. Therefore, we performed time-course microarray analysis to explore the molecular mechanisms of anastasis during reversal of ethanol-induced apoptosis in mouse primary liver cells. We found striking changes in transcription of genes involved in multiple pathways, including early activation of pro-survival genes, cell cycle arrest, stress-inducible responses, and at delayed times, cell migration and angiogenesis. Here, we present the time-course whole-genome gene expression dataset revealing gene expression profiles during the reversal of apoptosis. This dataset provides important insights into the physiological, pathological, and therapeutic implications of anastasis.

scholarly journals Essential Role of Endogenous MOZ in Aberrant HoxA9 and Meis1 Expressions Induced By MOZ Fusion Gene

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2191-2191
Author(s):  
Takuo Katsumoto ◽  
Kazutsune Yamagata ◽  
Yoko Ogawara ◽  
Takuro Nakamura ◽  
Issay Kitabayashi
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Molecular Mechanisms ◽  
Zinc Finger Protein ◽  
Conflicts Of Interest ◽  
Expression Profiles ◽  
Leukemia Cells ◽  
Hematopoietic Stem

Abstract Monocytic leukemia Zinc finger protein (MOZ), a histone acetyltransferase, is involved in chromosome translocations associated with FAB M4/M5 types of acute myeloid leukemia (AML). In normal hematopoiesis, MOZ is essential for self-renewal of hematopoietic stem cells (HSCs) and for expression of HoxA9/Meis1 in hematopoietic stem/progenitor cells (HSPCs). Previously we found that endogenous MOZ is critical for MOZ-TIF2-induced AML. Although MOZ-/- cells expressing the MOZ-fusion serially generated colonies in vitro, they did not induce AML after transplantation into recipient mice. In these cells, up-regulation of Meis1 was impaired, while HoxA9 expression was induced. However, roles of endogenous MOZ in MOZ fusion induced leukemia remained unclear. To elucidate molecular mechanisms, we performed experiments described below. First, to reveal mechanisms in defect of Meis1 expression in MOZ-/- MOZ-fusion leukemia cells, we performed chromatin immune-precipitation assays on Meis1 locus. Coincident with gene expression, active histone marks (H3K9ac, H3K27ac etc.) were disrupted. In contrast, repressive histone modifications (H3K9me2, H3K27me3) were elevated. Next we analyzed requirement of HoxA9 and Meis1 in MOZ fusion induced AML development. When mice were transplanted with MOZ-/- HSPCs simultaneously introduced with MOZ-fusion and Meis1 genes, AML development were induced. On the other hand, when Meis1 was conditionally deleted in MOZ-fusion leukemia cells, AML development was significantly delayed. Mice transplanted with MOZ-/- HSPCs, which were introduced with both HoxA9 and Meis1 genes elicited AML development. Furthermore, we analyzed gene expression profiles of MOZ-/- MOZ fusion leukemia cells. In these cells, expressions of monocyte/macrophage lineage characteristic genes (C/EBPa, Irf8, CD68 etc.) and MLL fusion target genes (Meis1, Mef2c) were decreased. In contract, other hematopoietic lineage characteristic genes (GATA1-3, FOG-1, CD41, Aiolos, Helios, Eag, Epx etc.) were increased. In addition, expression of CDK inhibitor INK4A was also up-regulated. Finally, we tested requirement of endogenous MOZ in various cellular conditions. Previous report showed that AML development was induced by introduction of MOZ-TIF2 not only in hematopoietic stem cells but also in more differentiated Common myeloid progenitors (CMPs) and Granulocyte/Monocyte progenitors (GMPs) (Huntly et al, Cancer Cell 2004). So we introduced MOZ fusion genes in HSCs and CMPs collected from E14.5 MOZ-/- fetal liver. MOZ-/- HSCs, not CMPs, expressing MOZ-TIF2 continuously formed colonies in vitro. In the CMPs expressing MOZ-TIF2, expression of both Meis1 and HoxA9, were abolished. These results suggest that high levels of HoxA9 and Meis1 expressions were respectively required for MOZ-TIF2-induced AML development, and that endogenous MOZ is critical for MOZ-TIF2-induced AML development. Disclosures No relevant conflicts of interest to declare.

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.

scholarly journals Transcriptome analysis of gravitational effects on mouse skeletal muscles under microgravity and artificial 1 g onboard environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Risa Okada ◽  
Shin-ichiro Fujita ◽  
Riku Suzuki ◽  
Takuto Hayashi ◽  
Hirona Tsubouchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Transcriptome Analysis ◽  
Fiber Type ◽  
Expression Profiles ◽  
Space Station ◽  
Gene Expression Profiles

AbstractSpaceflight causes a decrease in skeletal muscle mass and strength. We set two murine experimental groups in orbit for 35 days aboard the International Space Station, under artificial earth-gravity (artificial 1 g; AG) and microgravity (μg; MG), to investigate whether artificial 1 g exposure prevents muscle atrophy at the molecular level. Our main findings indicated that AG onboard environment prevented changes under microgravity in soleus muscle not only in muscle mass and fiber type composition but also in the alteration of gene expression profiles. In particular, transcriptome analysis suggested that AG condition could prevent the alterations of some atrophy-related genes. We further screened novel candidate genes to reveal the muscle atrophy mechanism from these gene expression profiles. We suggest the potential role of Cacng1 in the atrophy of myotubes using in vitro and in vivo gene transductions. This critical project may accelerate the elucidation of muscle atrophy mechanisms.

scholarly journals Cell–cell coupling and DNA methylation abnormal phenotypes in the after-hours mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Federico Tinarelli ◽  
Elena Ivanova ◽  
Ilaria Colombi ◽  
Erica Barini ◽  
Edoardo Balzani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Neuronal Networks ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Neuronal Cultures ◽  
Functional Impairments ◽  
After Hours ◽  
The Impact

Abstract Background DNA methylation has emerged as an important epigenetic regulator of brain processes, including circadian rhythms. However, how DNA methylation intervenes between environmental signals, such as light entrainment, and the transcriptional and translational molecular mechanisms of the cellular clock is currently unknown. Here, we studied the after-hours mice, which have a point mutation in the Fbxl3 gene and a lengthened circadian period. Methods In this study, we used a combination of in vivo, ex vivo and in vitro approaches. We measured retinal responses in Afh animals and we have run reduced representation bisulphite sequencing (RRBS), pyrosequencing and gene expression analysis in a variety of brain tissues ex vivo. In vitro, we used primary neuronal cultures combined to micro electrode array (MEA) technology and gene expression. Results We observed functional impairments in mutant neuronal networks, and a reduction in the retinal responses to light-dependent stimuli. We detected abnormalities in the expression of photoreceptive melanopsin (OPN4). Furthermore, we identified alterations in the DNA methylation pathways throughout the retinohypothalamic tract terminals and links between the transcription factor Rev-Erbα and Fbxl3. Conclusions The results of this study, primarily represent a contribution towards an understanding of electrophysiological and molecular phenotypic responses to external stimuli in the Afh model. Moreover, as DNA methylation has recently emerged as a new regulator of neuronal networks with important consequences for circadian behaviour, we discuss the impact of the Afh mutation on the epigenetic landscape of circadian biology.

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