Hyperthermia and p53 effects on global gene expressions
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11547 | GEO | 2009/05/01
SECONDARY ACCESSION(S): PRJNA106273
REPOSITORIES: GEO
Similar Datasets
Project description:Neural tube defects (NTDs) are one of the most common human birth defects, with a prevalence of approximately 1 in 1000 live births in the United States. In animal studies, deletion of p53 leads to a significant increase in embryos that exhibit exencephaly. Whereas several studies have closely investigated the morphological changes of p53-deficient embryos, there is no study that has reported the molecular-level alternations in p53-deficient embryos. Here we use microarray approach to find genes modified by deletion of p53 in day 8.5 mouse embryos to identify genes that may be involved in the mechanisms underlining NTDs and begin to define the developmental role of p53 in the etiology of NTDs. Keywords: genetic modification
2009-05-01 | GSE11321 | GEO
Project description:This data series was used for two separate studies. The initial study was aimed to idenify expression changes brought about by the Cecr2Gt45Bic mutation during neural closure. The study included two different strains, BALB/cCrl in which Cecr2GT45Bic shows a neural tube defect phenotype and FVB/N in which Cecr2Gt45Bic does not manifest neural closure defects. The second was to idenify strain specific expression differences present during neural closure of the mouse embryo between BALB/cCrl and FVB/N in order to identify candidate modifiers of the Cecr2Gt45Bic neural tube defect. Relevant abstracts are included below. The initial study ; BACKGROUND: Over 200 mouse genes are associated with neural tube defects (NTDs), including Cecr2, the bromodomain-containing subunit of the CERF chromatin remodeling complex. METHODS: Gene-trap mutation Cecr2Gt45Bic results in 74% exencephaly (equivalent of human anencephaly) on the BALB/c strain. Gene expression altered during cranial neural tube closure by the Cecr2 mutation was identified through microarray analysis of 11M-bM-^@M-^S14 somites stage Cecr2Gt45Bicembryos. RESULTS: Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts up-regulated and 54 transcripts down-regulated in the Cecr2Gt45Bic embryos (fold > 1.5, p < 0.05). The Cecr2 transcript was reduced only M-bM-^HM-<7- to 14-fold from normal levels, suggesting the Cecr2Gt45Bic is a hypomorphic mutation. We therefore generated a novel Cecr2 null allele (Cecr2tm1.1Hemc). Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2Gt45Bic in both BALB/c and FVB/N strains, in addition to midline facial clefts and forebrain encephalocele in the FVB/N strain. The Cecr2 transcript is reduced 260-fold in the Cecr2tm1.1Hemc line. Subsequent qRT-PCR using Cecr2tm1.1Hemc mutant heads confirmed downregulation of transcription factors Alx1/Cart1,Dlx5, Eya1, and Six1. CONCLUSIONS: As both Alx1/Cart1 and Dlx5 mouse mutations result in exencephaly, we hypothesize that changes in expression of these mesenchymal/ectodermal transcription factors may contribute to NTDs associated with Cecr2. Birth Defects Research (Part A), 2010. 010 Wiley-Liss, Inc. The second study: ABSTRACT:Although neural tube defects (NTDs) are common in humans, little is known about their multifactorial genetic causes. While most mouse models involve NTDs caused by a single mutated gene, we have previously described a multigenic system involving susceptibility to NTDs. In mice with a mutation in Cecr2, the cranial NTD exencephaly shows strain specific differences in penetrance, with 74% penetrance in BALB/cCrl and 0% penetrance in FVB/N. Whole genome linkage analysis showed that a region of chromosome 19 was partially responsible for this difference in penetrance. We now reveal by genetic analysis of three subinterval congenic lines that the chromosome 19 region contains more than one modifier gene. Analysis of embryos showed that although a Cecr2 mutation causes wider neural tubes in both strains, FVB/N embryos overcome this abnormality and close. A microarray analysis comparing neurulating female embryos from both strains identified differentially expressed genes within the chromosome 19 region, including Arhgap19, which is expressed at a lower level in BALB/cCrl due to a stop codon specific to that substrain. Modifier genes in this region are of particular interest because it is syntenic to human chromosome 10q25, the site of a human susceptibility locus. (MANUSCRIPT PENDING SUBMISSION) Thieler STAGE 13-14 (11-14 somite) female embryos where disected away from extraembryonic membranes for RNA extraction and hybridization on Affymetrix microarrays. A single embryo was processed per array, with four biological replicates per genotype BALB/cCrl, Cecr2GT45Bic BALB/cCrl, FVB/N, and Cecr2Gt45Bic FVB/N.
2012-02-27 | E-GEOD-30957 | biostudies-arrayexpress
Project description:This data series was used for two separate studies. The initial study was aimed to idenify expression changes brought about by the Cecr2Gt45Bic mutation during neural closure. The study included two different strains, BALB/cCrl in which Cecr2GT45Bic shows a neural tube defect phenotype and FVB/N in which Cecr2Gt45Bic does not manifest neural closure defects. The second was to idenify strain specific expression differences present during neural closure of the mouse embryo between BALB/cCrl and FVB/N in order to identify candidate modifiers of the Cecr2Gt45Bic neural tube defect. Relevant abstracts are included below. The initial study ; BACKGROUND: Over 200 mouse genes are associated with neural tube defects (NTDs), including Cecr2, the bromodomain-containing subunit of the CERF chromatin remodeling complex. METHODS: Gene-trap mutation Cecr2Gt45Bic results in 74% exencephaly (equivalent of human anencephaly) on the BALB/c strain. Gene expression altered during cranial neural tube closure by the Cecr2 mutation was identified through microarray analysis of 11–14 somites stage Cecr2Gt45Bicembryos. RESULTS: Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts up-regulated and 54 transcripts down-regulated in the Cecr2Gt45Bic embryos (fold > 1.5, p < 0.05). The Cecr2 transcript was reduced only ∼7- to 14-fold from normal levels, suggesting the Cecr2Gt45Bic is a hypomorphic mutation. We therefore generated a novel Cecr2 null allele (Cecr2tm1.1Hemc). Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2Gt45Bic in both BALB/c and FVB/N strains, in addition to midline facial clefts and forebrain encephalocele in the FVB/N strain. The Cecr2 transcript is reduced 260-fold in the Cecr2tm1.1Hemc line. Subsequent qRT-PCR using Cecr2tm1.1Hemc mutant heads confirmed downregulation of transcription factors Alx1/Cart1,Dlx5, Eya1, and Six1. CONCLUSIONS: As both Alx1/Cart1 and Dlx5 mouse mutations result in exencephaly, we hypothesize that changes in expression of these mesenchymal/ectodermal transcription factors may contribute to NTDs associated with Cecr2. Birth Defects Research (Part A), 2010. 010 Wiley-Liss, Inc. The second study: ABSTRACT:Although neural tube defects (NTDs) are common in humans, little is known about their multifactorial genetic causes. While most mouse models involve NTDs caused by a single mutated gene, we have previously described a multigenic system involving susceptibility to NTDs. In mice with a mutation in Cecr2, the cranial NTD exencephaly shows strain specific differences in penetrance, with 74% penetrance in BALB/cCrl and 0% penetrance in FVB/N. Whole genome linkage analysis showed that a region of chromosome 19 was partially responsible for this difference in penetrance. We now reveal by genetic analysis of three subinterval congenic lines that the chromosome 19 region contains more than one modifier gene. Analysis of embryos showed that although a Cecr2 mutation causes wider neural tubes in both strains, FVB/N embryos overcome this abnormality and close. A microarray analysis comparing neurulating female embryos from both strains identified differentially expressed genes within the chromosome 19 region, including Arhgap19, which is expressed at a lower level in BALB/cCrl due to a stop codon specific to that substrain. Modifier genes in this region are of particular interest because it is syntenic to human chromosome 10q25, the site of a human susceptibility locus. (MANUSCRIPT PENDING SUBMISSION)
2012-02-27 | GSE30957 | GEO
Project description:Neural tube defects (NTDs) are common birth defects in humans and show an unexplained female bias. Female mice lacking the tumor suppressor p53 display NTDs with incomplete penetrance. We found that the combined loss of pro-apoptotic BIM and p53 caused 100% penetrant, female-exclusive NTDs, which allowed us to investigate the female-specific functions of p53. We report that female p53–/– neural tube samples show fewer cells with inactive X markers Xist and H3K27me3, and a concomitant increase in biallelic expression of the X-linked genes, Huwe1 and Usp9x. The depletion of Xist and increase X-linked gene expression was confirmed by RNA sequencing.
2019-03-26 | GSE127446 | GEO
Project description:A deeper mechanistic understanding of response to hyperthermia in cancer cells in comparison between hyperthermia sensitive and resistant ovarian cancer cell lines
2016-12-31 | GSE77310 | GEO
Project description:Morphogenesis of the mammalian neural tube (NT) is reliant on precise, spatio-temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube defects (NTDs). MicroRNAs (miRNAs) as well as their downstream messenger RNA (mRNA) targets are key modulators of cell and tissue differentiation. To define potential roles of miRNAs and mRNAs in development of the murine neural tube (NT), total RNA preparations from gestation day (GD)-8.5, -9.0 and -9.5 (crtitcal period of NT developemnt) mouse embryos were used to hybridize both microRNA arrays and messenger RNA arrays, to identify miRNAs and mRNAs co-expressed in the same developing NT tissue samples.
2022-11-13 | GSE140776 | GEO
Project description:Morphogenesis of the mammalian neural tube (NT) is reliant on precise, spatio-temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube defects (NTDs). MicroRNAs (miRNAs) as well as their downstream messenger RNA (mRNA) targets are key modulators of cell and tissue differentiation. To define potential roles of miRNAs and mRNAs in development of the murine neural tube (NT), total RNA preparations from gestation day (GD)-8.5, -9.0 and -9.5 (crtitcal period of NT developemnt) mouse embryos were used to hybridize both microRNA arrays and messenger RNA arrays, to identify miRNAs and mRNAs co-expressed in the same developing NT tissue samples.
2022-11-13 | GSE140775 | GEO
Project description:In order to more thoroughly investigate the mechanism of arsenate-induced NTDs we designed experiment in which highly sensitive Folr2 nullizygous mice were treated i.p. with teratogenic dose of sodium arsenate just at the beginning of the neural tube formation process. This specific knockout mouse and arsenic exposure conditions were chosen as they warranted high incidence of exencephaly in exposed embryos. We investigated the gene expression changes induced by arsenic in the anterior part of neural tube in order to discover patterns that might shed light on the mechanism of arsenic’s teratogenicity. Keywords: toxic response
2005-12-30 | GSE3412 | GEO
Project description:The rationale underlying hyperthermia is the fact that temperatures over 42.5˚C are highly cytotoxic to tumor cells. On the other hand, although mild hyperthermia at a range from 39 to 41˚C alone did not induce cytotoxicity in tumor cells, mild hyperthermia is reported to show a synergism with radiotherapy and anti-cancer drugs. Here, the effects of mild hyperthermia (41˚C for 30 min) on the gene expression in human lymphoma U937 cells were investigated using by an Affymetrix GeneChip system. Although the cells treated with the mild hyperthermia did not induce apoptosis, a significant increase in protein levels of heat shock proteins, Hsp40 and Hsp70, was observed following activation of heat shock factor-1. At 3 h post-treatment, 938 probe sets that were differentially expressed by >1.5-fold were identified. Keywords: mild hyperthermia, gene expression, Human lymphoma U937 cell
2008-01-03 | GSE10043 | GEO
Project description:Physical factors can have major influences on the proliferation and differentiation fate of hematopoietic stem cells in culture. Recently, we demonstrated that cord blood CD34+ cells undergo accelerated and increased megakaryocyte differentiation when incubated at 39°C. In this study, we investigated in detail the impacts of mild hyperthermia on the kinetics of megakaryocyte differentiation, maturation, polyploidization and cell viability. The qualitative and quantitative effects on Mk differentiation were found to be rapidly induced, and optimization of the culture length at 39°C led to greater Mk yields. Mild hyperthermia did not promote endomitosis of cord blood-derived Mk, but rather led to a small reduction in the proportion of polyploid Mk. Moreover, it had little impact on viability but induced a significant shift in the proportion of cells undergoing apoptosis at 37°C to necrosis at 39°C. Finally, our results suggest that the effects on megakaryocyte differentiation could be the consequences of aberrant expression of key megakaryocyte transcription factors induced by mild hyperthermia. Keywords: Effect of mild hyperthermia on Mk differentiation
2007-12-01 | GSE9218 | GEO