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Total 806 record(s) from BioProject
- Accession: PRJNA612190
- Title: Tp53 suppression promotes cardiomyocyte proliferation during zebrafish heart regeneration
- Description: Transcriptome sequencing of uninjured and regenerating (7dpi) tp53M214K and tp53WT ventricles.
Overall design: 4 experimental groups were analyzed in triplicates: 1) uninjured ventricle of tp53 mutant fish; 2) injured ventricle of tp53 mutant fish; 3) uninjured ventricle of tp53 wild type fish; 4) injured ventricle of tp53 wild type fish.
- BasicInfo : PRJNA612190; Transcriptome or Gene expression; ModelOrganism
- Accession: PRJNA663474
- Title: Next Generation Sequencing Facilitates Quantitative Analysis of TP53-WT and TP53-KO HCT116 cells transcriptomes [RNA-seq]
- Description: Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare TP53-WT and TP53-KO HCT116 cells transcriptome profiling (RNA-seq) under 5-FU treatment condition and to evaluate the correlation between transcriptome profileing and chromatin accessibility under 5-FU treatment.
Methods: HCT116 cell profiles of TP53-WT and TP53- KO were generated by deep sequencing, in duplicates, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform levels: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA).
Conclusions: Our study represents the detailed analysis of TP53-WT and TP53-KO HCT116 cell transcriptomes under 5-FU treatment with different timepoint, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that RNA-seq offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a TP53-WT and TP53-KO cells with and without 5-FU treatment in different timepoint. We conclude that NGS based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.
Overall design: 5-FU treated and non-treated mRNA profiles of TP53-WT and TP53-KO cells in different timepoint.
- BasicInfo : PRJNA663474; Transcriptome or Gene expression; Medical
- Accession: PRJNA756361
- Title: TP53 loss initiates chromosomal instability in fallopian tube epithelial cells
- Description: High-grade serous ovarian cancer originates in the fallopian tube and is characterized by ubiquitous mutations in TP53. Here, we generated TP53 single-, TP53/BRCA1 and TP53/MYC double- and TP53/BRCA1/MYC triple-mutant subclones of the fallopian tube-derived cell line FNE1 using CRISPR/Cas9. These mutant subclones were subsequently subjected to RNA sequencing to determine the impact of these oncogenic mutations on signaling pathways.
Overall design: RNA sequencing of 27 fallopian tube-derived cell lines.
- BasicInfo : PRJNA756361; Transcriptome or Gene expression; Medical
- Accession: PRJNA708340
- Title: TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling [ChIP-seq]
- Description: NGS was used to analyze role of TP53 in differentiation of human embryonic stem cells. TP53, a transcription factor, binds DNA and regulates transcription of specific genes. Chipseq of TP53 was done on WT ESCs and NPCs to identify direct targets of TP53 during differentiation of hESCs into neuronal lineage.
Overall design: TP53 target genes in WT hESCs and in vitro differentiated NPCs were obtained.
- BasicInfo : PRJNA708340; Epigenomics; Medical
- Accession: PRJNA498696
- Title: Defining TP53 pioneering capabilities with competitive nucleosome binding assays
- Description: Accurate gene expression requires the targeting of transcription factors (TFs) to regulatory sequences often occluded within nucleosomes. The ability to target a transcription factor binding site (TFBS) within a nucleosome has been the defining characteristic for a special class of TFs known as pioneer factors. Recent studies suggest TP53 functions as a pioneer factor that can target its TFBS within nucleosomes, but it remains unclear how TP53 binds to nucleosomal DNA. To comprehensively examine TP53 nucleosome binding we competitively bound TP53 to multiple in vitro formed nucleosomes containing a high or low-affinity TP53 TFBS located at differing translational and rotational positions within the nucleosome. Stable TP53-nucleosome complexes were isolated and quantified using next generation sequencing. Our results demonstrate TP53 binding is limited to nucleosome edges with significant binding inhibition occurring within 50-bp of the nucleosome dyad. Binding site affinity only affects TP53 binding for TFBS located at the same nucleosomal positions, otherwise nucleosome position takes precedence. Furthermore, TP53 has strong non-specific nucleosome binding facilitating its interaction with chromatin. Our in vitro findings were confirmed by examining TP53 induced binding in a cell line model, showing induced binding at nucleosome edges flanked by a nucleosome free region. Overall, our results suggest that the pioneering capabilities of TP53 are driven by non-specific nucleosome binding with specific binding at nucleosome edges.
- BasicInfo : PRJNA498696; Raw sequence reads; Medical
- Accession: PRJNA309083
- Title: Compare proB cells from WT, Tp53-/-, Lnk-/-, Tp53-/-Lnk-/- mice and Tp53-/-Lnk-/-B-ALL
- Description: The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies.
Overall design: B220+CD19+CD43+AA4.1+IgM-NK1.1-Ly6c- bone marrow proB cells were double sorted from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the PENN Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 2.0ST array (Affymetrix).
- BasicInfo : PRJNA309083; Transcriptome or Gene expression; ModelOrganism
- Accession: PRJNA102101
- Title: Genomic profiling of TP53 and non-TP53 Li-Fraumeni syndrome tumors reveals hits in the p53 and overlapping pathways
- Description: Li-Fraumeni syndrome (LFS) is a rare, clinically and genetically heterogeneous inherited cancer syndrome. Most cases are due to mutations in TP53. CHK2 is a minor predisposing locus; we recently mapped a third locus to 1q23. In both TP53 and non-TP53 LFS, there is evidence for risk heterogeneity within and between kindreds, suggesting additional risk modifiers. Using BAC- and SNP-based microarrays, we performed genomic profiling of primary soft tissue sarcomas, osteosarcomas and matching constitutive samples of 10 LFS patients (6 with and 4 without TP53 mutations), to identify genome-wide patterns of copy number changes and loss-of-heterozygosity (LOH). Our complementing global approaches revealed several interesting patterns for TP53 and non-TP53 LFS tumors, including positive (1q/7, 3p/15, 4q/9q, 8q/19p, 9p/10q, 13/14 and 15q/18q) and negative (2q/9q, 3q/14q and 4q/6q) associations between chromosomal regions. The region containing the oncogene TWIST1 (7p21.1) was the most common gain independent of TP53 status and tumor type, while LOH of 8q11.2 with the tumor suppressor ST18 was the only region exclusively associated with non-TP53 soft tissue sarcomas. We resequenced known mutations in BRAF, KRAS and NRAS and identified somatic NRAS mutations in 2 of 10 tumors. TP53 and non-TP53 LFS tumors shared multiple hits in genes of the p53 and overlapping pathways. Although common dogma in cancer genetics holds that multiple hits in the same pathway are redundant and thus unlikely, we show that different combinations of genetic alterations in both TP53 and non-TP53 LFS tumors appear to act together in the p53 network in LFS tumorigenesis
Keywords: Comparative genomic hybridization
Overall design: Using the Spectral Genomics dye-swap BAC arrays we studied 10 Li Fraumeni syndrome tumor cases
- BasicInfo : PRJNA102101; Variation; Medical
- Accession: PRJNA547633
- Title: Hierarchy of mono- and bi-allelic TP53 alterations in Multiple Myeloma cell fitness
- Description: Comparison of the TP53 wild-type myeloma cell line AMO1 with the CRISPR/Cas9 engineered AMO1 cell line named UMC901. UMC901 harbors bi-allelic alterations to TP53: TP53 del/mut. Analysis of impact of TP53 alterations on gene transcription and identification of affected pathways by transcriptome-wide differential gene expression analysis.
Overall design: Triplicates for each cell line, comparison of UMC901 against AMO1 as reference. Circa 50 million single-end 75 nt reads per sample
- BasicInfo : PRJNA547633; Transcriptome or Gene expression; Medical
- Accession: PRJNA396062
- Title: Transcriptome analysis of TP53-R248L overexpressed 19NS patient-derived glioblastoma cells
- Description: This study demonstrates the role of TP53 gain-of-function (GOF) mutation on glioblastoma progression. However, little is known about the transcriptional alteration upon TP53 GOF mutation. In this study, we found that TP53 GOF mutation (R248L mutation) promotes the enrichment of multiple gene signatures related to inflammation and chemotaxis. Particularly, through in vitro and in vivo approaches, we verified that TP53 GOF mutation enhances NFKB signaling which in turn up-regulates CCL2 and TNFA. Taken together, these results suggest the function of TP53 GOF mutation driving aggressiveness of malignant brain tumor.
Overall design: A patient-derived glioblastoma cell line 19NS was transfected with pLL CMV puro (19NS-control) or pLL CMV TP53-R248L puro (19NS-TP53-R248L). The 3 biological replicates of RNA extracts in these cells was used for transcriptome analysis.
- BasicInfo : PRJNA396062; Transcriptome or Gene expression; Medical