scholarly journals Genetic Modifier Screens on Hairless Gain-of-Function Phenotypes Reveal Genes Involved in Cell Differentiation, Cell Growth and Apoptosis in Drosophila melanogaster

Genetics ◽  
2005 ◽  
Vol 171 (3) ◽  
pp. 1137-1152 ◽  
Author(s):  
Dominik Müller ◽  
Sabrina J. Kugler ◽  
Anette Preiss ◽  
Dieter Maier ◽  
Anja C. Nagel
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Differentiation ◽  
Cell Growth ◽  
Genetic Modifier ◽  
Gain Of Function

scholarly journals Combination Treatment with GSK126 and Pomalidomide Induces B-Cell Differentiation in EZH2 Gain-of-Function Mutant Diffuse Large B-Cell Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2541
Author(s):  
Sungryul Park ◽  
Seung-Hyun Jo ◽  
Jong-Hwan Kim ◽  
Seon-Young Kim ◽  
Jae Du Ha ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Zinc Finger ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
B Cell Differentiation ◽  
Gain Of Function ◽  
Polycomb Repressive Complex 2 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), regulates genes involved in cell lineage and differentiation through methylating lysine 27 on histone H3 (H3K27me3). Recurrent gain-of-function mutations of EZH2 have been identified in various cancer types, in particular, diffuse large B-cell lymphoma (DLBCL), through large-scale genome-wide association studies and EZH2 depletion or pharmacological inhibition has been shown to exert an antiproliferative effect on cancer cells, both in vitro and in vivo. In the current study, a combination of pomalidomide and GSK126 synergistically inhibited the growth of EZH2 gain-of-function mutant Diffuse large B-cell lymphoma (DLBCL) cells. Furthermore, this synergistic effect appeared to be dependent on cereblon (CRBN), a cellular receptor of pomalidomide, but not degradation of IKAROS family zinc finger 1 (IKZF1) or IKAROS family zinc finger 3 (IKZF3). RNA sequencing analyses revealed that co-treatment with GSK126 and pomalidomide induced specific gene sets involved in B-cell differentiation and apoptosis. Synergistic growth inhibition and B-cell differentiation were further validated in xenograft mouse models. Our collective results provide a molecular basis for the mechanisms underlying the combined therapeutic effects of PRC2 inhibitors and pomalidomide on EZH2-mutated DLBCL.

scholarly journals Effects of low-to-moderate ethanol consumption on colonic growth and gene expression in young adult and middle-aged male rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243499
Author(s):  
Nicole Wells ◽  
Jacqueline Quigley ◽  
Jeremy Pascua ◽  
Natalie Pinkowski ◽  
Lama Almaiman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Young Adult ◽  
Cell Growth ◽  
Alcohol Consumption ◽  
Ethanol Consumption ◽  
Ethanol Treatment ◽  
Middle Aged

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk or may provide a protective effect reducing colorectal cancer risk. Prior research highlights the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. The present study investigated whether chronic low-to-moderate ethanol consumption altered these parameters of colonic cell growth and expression of related genes. Twenty-four nondeprived young adult (109 days old) and 24 nondeprived middle-aged (420 days old) Wistar rats were randomly assigned to an ethanol-exposed or a water control group (n = 12/group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks. Colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki-67, goblet cell and TUNEL, respectively. Gene expression of cyclin D1 (Ccnd1), Cdk2, Cdk4, p21waf1/cip1 (Cdkn1a), E-cadherin (Cdh1) and p53 were determined by quantitative real-time polymerase chain reaction in colonic scraped mucosa. Ethanol treatment resulted in a lower cell proliferation index and proliferative zone, and lower Cdk2 expression in both age groups, as well as trends toward lower Ccnd1 and higher Cdkn1a expression. Cell differentiation was modestly but significantly reduced by ethanol treatment only in older animals. Overall, older rats showed decreases in apoptosis and gene expression of Cdk4, Cdh1, and p53 compared to younger rats, but there was no observed effect of ethanol exposure on these measures. These findings suggest that low-to-moderate ethanol consumption improves at least one notable parameter in colonic tumorigenesis (cell proliferation) and associated gene expression regardless of age, however, selectively decreased cell differentiation among older subjects.

Rat bone marrow derived mesenchymal progenitor cells support mouse ES cell growth and germ-like cell differentiation

2009 ◽  
Vol 33 (3) ◽  
pp. 434-441 ◽  
Author(s):  
Guanghui Cui ◽  
Zhengyu Qi ◽  
Xin Guo ◽  
Jie Qin ◽  
Yaoting Gui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
Cell Growth ◽  
Progenitor Cells ◽  
Es Cell ◽  
Mesenchymal Progenitor Cells ◽  
Rat Bone ◽  
Mouse Es Cell

PIK3CA-Related Overgrowth Spectrum

2019 ◽  
pp. 217-240
Author(s):  
Kim M. Keppler-Noreuil
Keyword(s):  
Cell Growth ◽  
Clinical Features ◽  
Tissue Specificity ◽  
Phenotypic Variability ◽  
Akt Pathway ◽  
Gain Of Function ◽  
Clinical Phenotypes ◽  
Segmental Overgrowth ◽  
Postzygotic Mutations ◽  
Cell Growth And Proliferation

Postzygotic mutations of the PIK3CA gene are associated with a series of clinical phenotypes characterized by segmental overgrowth and recently grouped under the term PIK3CA-related overgrowth spectrum (PROS). This chapter provides an overview of the clinical features shared by the phenotypes in PROS, including both the conditions with isolated features and the ones with syndromal presentation. The somatic overgrowth in cases with PROS is asymmetric, progressive, and “ballooning” in appearance and tends to involve predominantly the limbs, including fingers and toes, although the trunk and face are often affected as well. The tissues affected in the overgrowth can include all or some of these types: fibrous, adipose, vascular, nervous, and skeletal. Somatic gain-of-function mutations of PIK3CA cause activation of the PI3K-AKT pathway, leading to excessive cell growth and proliferation. Timing of PIK3CA mutations, tissue specificity, and type of mutation may play a role in the phenotypic variability of PROS.

scholarly journals dSETDB1 and SU(VAR)3–9 Sequentially Function during Germline-Stem Cell Differentiation in Drosophila melanogaster

PLoS ONE ◽  
2008 ◽  
Vol 3 (5) ◽  
pp. e2234 ◽  
Author(s):  
Jeongheon Yoon ◽  
Kyu-Sun Lee ◽  
Jung Sun Park ◽  
Kweon Yu ◽  
Sang-Gi Paik ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Germline Stem Cell

Mitogen-activated protein kinase pathway inhibitors rescue lethal phenotypes in a BRAF gain-of-function Drosophila melanogaster model

2018 ◽  
Vol 31 (4) ◽  
pp. 545-548 ◽  
Author(s):  
Anna Volkhardt ◽  
Jens Bohnekamp ◽  
Isabelle Pfeifle ◽  
Christoph Engel ◽  
Thomas M. Magin ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Gain Of Function ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 173 ◽  
Author(s):  
Gergely I. B. Varga ◽  
Gábor Csordás ◽  
Gyöngyi Cinege ◽  
Ferenc Jankovics ◽  
Rita Sinka ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Differentiation ◽  
Blood Cell ◽  
Cell Fate ◽  
Blood Cells ◽  
Mutational Analysis ◽  
Genetic Interaction ◽  
Lymph Gland ◽  
Loss Of Function ◽  
Hematopoietic Stem

Due to the evolutionary conservation of the regulation of hematopoiesis, Drosophila provides an excellent model organism to study blood cell differentiation and hematopoietic stem cell (HSC) maintenance. The larvae of Drosophila melanogaster respond to immune induction with the production of special effector blood cells, the lamellocytes, which encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result of a concerted action of all three hematopoietic compartments of the larva: the lymph gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland, the communication of the functional zones, the maintenance of HSC fate, and the differentiation of effector blood cells are regulated by a complex network of signaling pathways. Applying gene conversion, mutational analysis, and a candidate based genetic interaction screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor HECA in the hematopoiesis of Drosophila. We found that naive loss-of-function hdc mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector blood cell differentiation. We demonstrate that hdc genetically interacts with the Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph gland. By adding further details to the model of blood cell fate regulation in the lymph gland of the larva, our findings contribute to the better understanding of HSC maintenance.

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