Diallyl trisulphide, a H 2 S donor, compromises the stem cell phenotype and restores thyroid‐specific gene expression in anaplastic thyroid carcinoma cells by targeting AKT‐SOX2 axis

2021 ◽  
Author(s):  
Li Zhang ◽  
Shichen Xu ◽  
Xian Cheng ◽  
Jiangxia Zheng ◽  
Yunping Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Stem Cell Phenotype

scholarly journals Tissue-specific gene expression in medullary thyroid carcinoma cells employing calcitonin regulatory elements and AAV vectors

2001 ◽  
Vol 8 (7) ◽  
pp. 469-472 ◽  
Author(s):  
Shiming Jiang ◽  
Annette Altmann ◽  
Dirk Grimm ◽  
Jürgen A Kleinschmidt ◽  
Tobias Schilling ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Regulatory Elements ◽  
Carcinoma Cells ◽  
Specific Gene ◽  
Tissue Specific ◽  
Medullary Thyroid ◽  
Tissue Specific Gene ◽  
Specific Gene Expression

WNT/β-Catenin Signaling Affects Cell Lineage and Pluripotency-Specific Gene Expression in Bovine Blastocysts: Prospects for Bovine Embryonic Stem Cell Derivation

2015 ◽  
Vol 24 (20) ◽  
pp. 2437-2454 ◽  
Author(s):  
Zofia Eliza Madeja ◽  
Kamila Hryniewicz ◽  
Maciej Orsztynowicz ◽  
Piotr Pawlak ◽  
Anna Perkowska
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Stem Cell Derivation

scholarly journals Ush regulates hemocyte-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis

2020 ◽  
Author(s):  
Jonathan Lenz ◽  
Robert Liefke ◽  
Julianne Funk ◽  
Samuel Shoup ◽  
Andrea Nist ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cell ◽  
Specific Gene ◽  
Cell Cycle Regulators ◽  
Cell Type ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Specific Gene Expression ◽  
Cell Type Specific

AbstractThe generation of lineage-specific gene expression programmes that alter proliferation capacity, metabolic profile and cell type-specific functions during differentiation from multipotent stem cells to specialised cell types is crucial for development. During differentiation gene expression programmes are dynamically modulated by a complex interplay between sequence-specific transcription factors, associated cofactors and epigenetic regulators. Here, we study U-shaped (Ush), a multi-zinc finger protein that maintains the multipotency of stem cell-like hemocyte progenitors during Drosophila hematopoiesis. Using genomewide approaches we reveal that Ush binds to promoters and enhancers and that it controls the expression of three gene classes that encode proteins relevant to stem cell-like functions and differentiation: cell cycle regulators, key metabolic enzymes and proteins conferring specific functions of differentiated hemocytes. We employ complementary biochemical approaches to characterise the molecular mechanisms of Ush-mediated gene regulation. We uncover distinct Ush isoforms one of which binds the Nucleosome Remodeling and Deacetylation (NuRD) complex using an evolutionary conserved peptide motif. Remarkably, the Ush/NuRD complex specifically contributes to the repression of lineage-specific genes but does not impact the expression of cell cycle regulators or metabolic genes. This reveals a mechanism that enables specific and concerted modulation of functionally related portions of a wider gene expression programme. Finally, we use genetic assays to demonstrate that Ush and NuRD regulate enhancer activity during hemocyte differentiation in vivo and that both cooperate to suppress the differentiation of lamellocytes, a highly specialised blood cell type. Our findings reveal that Ush coordinates proliferation, metabolism and cell type-specific activities by isoform-specific cooperation with an epigenetic regulator.

Differentiation: the selective potentiation of chromatin domains

Development ◽  
1998 ◽  
Vol 125 (23) ◽  
pp. 4749-4755 ◽  
Author(s):  
J.A. Kramer ◽  
J.R. McCarrey ◽  
D. Djakiew ◽  
S.A. Krawetz
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Spermatogonial Stem Cell ◽  
Specific Gene ◽  
Cell Type ◽  
Chromatin Domains ◽  
Tissue Specific ◽  
Specific Gene Expression ◽  
Cell Type Specific ◽  
Cellular Phenotypes

Potentiation is requisite for the expression of our genome. It is the mechanism of opening chromatin domains to render genes accessible to tissue-specific and ubiquitous transacting-factors that enables transcription. The results presented in this study demonstrate that modulation of stage- and cell-type-specific gene expression during mammalian spermatogenesis involves selective potentiation of testis-expressed genes that reverses their repressive state when present in the spermatogonial stem cell. This directly contrasts hematopoiesis, which acts to selectively restrict lineage potential during differentiation from its permissive stem cell. These results are key to understanding how differentiative pathways are controlled and cellular phenotypes determined. A window to their modulation is presented.

Uniform Expression of Notch1, Suppressor of B-Cell–Specific Gene Expression, in Plasmablastic Lymphoma

2011 ◽  
Vol 135 (6) ◽  
pp. 770-775
Author(s):  
Adam C. Seegmiller ◽  
Huan-You Wang ◽  
Christa Hladik ◽  
Weina Chen
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Plasma Cell ◽  
Primary Effusion Lymphoma ◽  
Mtor Pathway ◽  
Plasmablastic Lymphoma ◽  
Cell Phenotype ◽  
Specific Gene ◽  
Plasma Cell Myeloma ◽  
Specific Gene Expression

Abstract Context.—Although the loss of B-lineage–specific gene expression is a distinctive feature of plasmablastic lymphoma, the underlying mechanism remains poorly understood. A candidate for this mechanism is Notch1 signaling, which interferes with the activity of B-cell–specific transcription factors E2A and early B-cell factor and positively regulates the mammalian target of rapamycin (mTOR) pathway. Objective.—To explore the mechanism of loss of B-cell phenotype by correlating expression of B-cell markers with that of Notch1 and downstream targets of the mTOR pathway in plasmablastic lymphoma. Design.—A combination of flow cytometric and immunohistochemical immunophenotyping techniques was used on 9 cases of plasmablastic lymphoma to correlate loss of B-cell markers with expression of Notch1 and downstream activation of the mTOR pathway. These results are compared with 5 cases of primary effusion lymphoma and 21 cases of plasma cell myeloma. Results.—Plasmablastic lymphoma cases exhibit nearly complete loss of B-cell–associated markers and uniform expression of Notch1, with a predominantly nuclear staining pattern. There is a concurrent activation of the mTOR pathway, indicated by expression of mTOR targets eukaryotic initiation factor 4E–binding protein 1 and phosphorylated ribosomal protein S6 in most cases. Similar results are seen in cases of primary effusion lymphoma and plasma cell myeloma. Conclusions.—These findings suggest that activation of Notch1 may be involved in suppression of B-cell–specific gene expression and global loss of the B-cell phenotype in plasmablastic lymphoma, similar to primary effusion lymphoma and plasma cell myeloma. Thus, there might be a role for the Notch1 and mTOR pathways in the pathogenesis and therapy of plasmablastic lymphoma.

scholarly journals CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation

Oncotarget ◽  
2016 ◽  
Vol 7 (36) ◽  
pp. 58351-58366 ◽  
Author(s):  
Yao-An Shen ◽  
Chia-Yu Wang ◽  
Hui-Yen Chuang ◽  
John Jeng-Jong Hwang ◽  
Wei-Hsin Chi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Nasopharyngeal Carcinoma ◽  
Cancer Stem Cell ◽  
Carcinoma Cells ◽  
Cell Phenotype ◽  
Cancer Stem Cell Phenotype ◽  
Stem Cell Phenotype

High Rate of FLT3 Mutations In Adult ETP-ALL.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1031-1031 ◽  
Author(s):  
Martin Neumann ◽  
Ebru Coskun ◽  
Ouidad Benlasfer ◽  
Sandra Heesch ◽  
Stefan Schwartz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Expression Pattern ◽  
Mirna Expression ◽  
Lymphoblastic Leukemia ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Gene Expression ◽  
Flt3 Mutation ◽  
Flt3 Mutations

Abstract Abstract 1031 Introduction: Mutations of FLT3 are recognized as important prognostic factor in acute myeloid leukemia (AML) with an impact on new therapeutic strategies. However, FLT3 mutations are rarely (1-3%) found in acute T-lymphoblastic leukemia (T-ALL). Recently, a new T-ALL subgroup defined by a specific gene expression profile and a characteristic immunophenotype (CD1a-, CD8-, CD5weak with expression of stem cell or myeloid markers) and with poor outcome has been described in pediatric T-ALL patients. This subgroup likely originates from early thymic progenitors (ETP) and has therefore been termed ETP-ALL. To unravel the molecular alterations of this distinct subgroup with myeloid characteristics, we studied adult ETP-ALL patients for FLT3 mutations. Moreover, we analyzed miRNA expression to explore their potential involvement in the specific gene expression signature observed in ETP-ALL. Patients and methods: We screened 1241 peripheral blood and bone marrow samples of T-ALL patients that were sent to the central diagnostic reference laboratory of the German Acute Lymphoblastic Leukemia Multicenter Study Group (GMALL). Of the immunophenotypically identified ETP-ALL patients (n=142), sufficient material was available in 70 cases. FLT3 mutations (ITD and TKD) were assessed using the FLT3 mutation assay (InVivoScribe Technologies, San Diego, USA). Expression of miRNAs was first screened by TaqMan low density arrays including 667 miRNAs in ETP-ALL (n=8) and compared to non-ETP T-ALL (n=6). Subsequently, expression of miR-221 and miR-222 was examined by real-time PCR in all 70 ETP-ALL. Results: In our cohort of 1241 T-ALL, 142 (11.4 %) patients showed an immunophenotype of an ETP-ALL, which is in the range of reported frequencies in pediatric patients. Among the 70 ETP-ALL samples analyzed, we identified 9 patients with a FLT3 D835 mutation and 15 patients with a FLT3 ITD. In total, 34 % (24 of the 70) patients carried a FLT3 mutation, which represents approximately 4 % of all T-ALL patients. In contrast, only one patient was identified with a FLT3 mutation within an arbitrarily selected control group of 107 T-ALL patients with a non-ETP immunophenotype. Interestingly, ETP-ALL with FLT3 mutations showed a distinct immunophentype compared to ETP-ALL with a wild type FLT3: ETP-ALL with FLT3 mutations had a higher rate of positivity for CD2 (88% vs. 30%, P<0.001), CD117 (83% vs. 28%, P<0.001), and CD13 (100 % vs. 37%, P<0.001). On the other hand, ETP-ALL with wild type FLT3 were characterized by a more frequent positivity of CD5 (54% vs. 4%, P<0.001) and CD33 (54% vs. 4%, P<0.001). Based on these findings a specific immunophenotype may be linked to FLT3 mutated ETP-ALL: in 73% (21/29) of patients with CD2/CD13 positivity a FLT3 mutation was present, compared to only 7% (3/41) of the remaining patients with ETP-ALL. In addition, we generated miRNA expression profiles in ETP-ALL and identified 7 miRNAs that were differentially expressed compared to non-ETP T-ALL. Among these miR-221 and miR-222, which were significantly overexpressed in ETP-ALL, are targeting genes characterizing the ETP-ALL phenotype (e.g. ETS1, KIT). Examination of miR-221 and miR-222 in 70 ETP-ALL revealed their particular overexpression in FLT3 mutated samples (miR-221 2.45-fold, P=0.012; miR-222: 2.05-fold, P=0.008) compared to ETP-ALL with wild type FLT3. Conclusion: We identified a yet unreported high frequency of FLT3 mutations in T-ALL, which are nearly exclusively found within the subgroup of ETP-ALL. In this group the rate is comparable high to the rate of FLT3 mutations in AML. Therefore, on the basis of established flow cytometry analysis we identified T-ALL patients that should be now prospectively and routinely screened for FLT3 mutations. Moreover, the distinct miRNA expression pattern may impact on the specific gene expression pattern of ETP-ALL. Thus, patients of this molecular distinct ETP-ALL entity may benefit from tyrosine kinase inhibitors in relapse situations or with presence of minimal residual disease as a bridging therapy to allogeneic stem cell transplantation. Disclosures: Baldus: Novartis: Research Funding.

Characterizing the clinical relevance of an embryonic stem cell phenotype in lung adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11001-11001
Author(s):  
M. M. Stevenson ◽  
W. Mostertz ◽  
C. Acharya ◽  
K. Walters ◽  
W. Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Lung Adenocarcinoma ◽  
Gene Expression Data ◽  
Embryonic Stem ◽  
Cell Phenotype ◽  
Expression Data ◽  
Stem Cell Phenotype

11001 Background: Cancer cells possess traits reminiscent of those ascribed to normal stem cells. It is unclear whether these phenotypic similarities between normal/embryonic stem cells and mature tumor cells, specific to lung cancer, are a result of underlying biologic processes, such as specific molecular pathways and regulatory networks. Methods: Using a large cohort of lung cancer cell lines with associated gene expression data, genes associated with an embryonic stem cell identity were used to develop a ‘signature’ representative of embryonic stemness (ES) activity specific to lung adenocarcinoma. Differential biology was evaluated using Gene Set Enrichment Analysis (GSEA) and signatures of oncogenic pathway deregulation. The ES signature was applied to three independent early (stage I - IIIa) lung adenocarcinoma data sets (N = 634) with clinically annotated gene expression data. The relationship between the ES phenotype and cisplatin sensitivity was also evaluated. Results: Using Bayesian regression analysis, a 100 gene signature representative of ES activity in lung adenocarcinoma was developed and validated in a leave-one-out-analysis. GSEA identified gene sets significantly represented in the ES signature: signature of neoplastic transformation, signature of undifferentiated cancer, BRCA pathway, and fibroblast serum response pathway, all associated with cancer invasiveness. Adenocarcinomas with ES demonstrated increased activation of RAS (p = 0.0002), MYC (p = 0.0057), wound healing (angiogenesis) (p < 0.0001), chromosomal instability (p < 0.0001), and invasiveness (p < 0.0001) gene signatures. Adenocarcinomas (N= 634) with ES had a decreased survival (p<0.04). The ES signature was not prognostic in prostate, ovarian, or breast adenocarcinomas. Lung tumors (N=634) and adenocarcinoma cell lines (N=31) with ES were more resistant to cisplatin (p<0.0001 and p=0.0063, respectively). Conclusions: Lung adenocarcinomas that share a common gene expression pattern with normal stem cells were associated with decreased survival and increased likelihood of resistance to cisplatin, indicating the aggressiveness of lung tumors with a stem cell phenotype. No significant financial relationships to disclose.

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