Ena-DATASET-MDACC-30-06-2020-22:22:29:973-1100 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006248 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:A mother/son pair with adult onset diploid AML were evaluated and found to have a dominant negative germline mutation in DNMT3A that is associated with global hypomethylation
| EGAS00001002940 | EGA
Project description:pre- and post-treatment sample pair Keywords: time-course
2003-04-21 | GSE231 | GEO
Project description:We characterized the role of the DNA methyltransferase DNMT3A in the fate decisions of murine megakaryocyte-biased HSCs and in the differentiation of megakaryocytes and platelets. In this experiment, we isolated washed platelets from 4 WT and 4 Dnmt3a+/– germline mice (2 males and 2 females per group) and subjected them to proteomic analysis by mass-spectrometry. We sought to identify changes at the protein level that occur in platelets due to aberrant DNA methylation during the differentiation of upstream hematopoietic cells.
2025-06-09 | PXD055265 | Pride
Project description:Complex genetic inheritance is thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human congenital heart defect, left ventricular non-compaction (LVNC), can be caused by a combination of rare, inherited heterozygous missense single nucleotide variants. Whole exome sequencing of a nuclear family revealed novel single nucleotide variants of MYH7 and MKL2 in an asymptomatic father while the offspring with severe childhood-onset LVNC harbored an additional missense variant in the cardiac transcription factor, NKX2-5, inherited from an unaffected mother. Mice bred to compound heterozygosity for the orthologous missense variants in Myh7 and Mkl2 had mild cardiac pathology; the additional inheritance of the Nkx2-5 variant yielded a more severe LVNC-like phenotype in triple compound heterozygotes. RNA sequencing identified genes associated with endothelial and myocardial development that were dysregulated in hearts from triple heterozygote mice and human induced pluripotent stem cell–derived cardiomyocytes harboring the three variants, with evidence for NKX2-5’s contribution as a modifier on the molecular level. These studies demonstrate that the deployment of efficient gene editing tools can provide experimental evidence for complex inheritance of human disease.
2019-05-31 | GSE111394 | GEO
Project description:Complex genetic inheritance is thought to underlie many human diseases, yet experimental proof of this model has been elusive. Here, we show that a human congenital heart defect, left ventricular non-compaction (LVNC), can be caused by a combination of rare, inherited heterozygous missense single nucleotide variants. Whole exome sequencing of a nuclear family revealed novel single nucleotide variants of MYH7 and MKL2 in an asymptomatic father while the offspring with severe childhood-onset LVNC harbored an additional missense variant in the cardiac transcription factor, NKX2-5, inherited from an unaffected mother. Mice bred to compound heterozygosity for the orthologous missense variants in Myh7 and Mkl2 had mild cardiac pathology; the additional inheritance of the Nkx2-5 variant yielded a more severe LVNC-like phenotype in triple compound heterozygotes. RNA sequencing identified genes associated with endothelial and myocardial development that were dysregulated in hearts from triple heterozygote mice and human induced pluripotent stem cell–derived cardiomyocytes harboring the three variants, with evidence for NKX2-5’s contribution as a modifier on the molecular level. These studies demonstrate that the deployment of efficient gene editing tools can provide experimental evidence for complex inheritance of human disease.
2019-05-31 | GSE131322 | GEO
Project description:Enzymes catalyzing CpG methylation in DNA, including DNMT1 and DNMT3A/B, are indispensable for mammalian tissue development and homeostasis. They are also implicated in human developmental disorders and cancers, supporting a critical role of DNA methylation during cell fate specification and maintenance. Recent studies suggest that histone post-translational modifications (PTMs) are involved in specifying patterns of DNMT localization and DNA methylation at promoters and actively transcribed gene bodies. However, mechanisms governing the establishment and maintenance of intergenic DNA methylation remain poorly understood. Germline mutations in DNMT3A lead to a childhood overgrowth syndrome that is phenotypically overlapping with Sotos syndrome caused by haploinsufficiency of NSD1, a histone methyltransferase catalyzing di-methylation on H3K36 (H3K36me2), pointing to a potential mechanistic link between the two disorders. Here we report that NSD1-mediated H3K36me2 is required for recruitment of DNMT3A and maintenance of DNA methylation at intergenic regions. Genome-wide analysis shows binding and activity of DNMT3A are co-localized with H3K36me2 at non-coding regions of euchromatin. Genetic ablation of NSD1 and its paralogue NSD2 in mouse and human cells redistributes DNMT3A to H3K36me3-marked gene bodies and reduces intergenic DNA methylation. NSD1 mutant tumors and Sotos patient samples are also associated with intergenic DNA hypomethylation. Consistently, PWWP-domain of DNMT3A shows dual recognition of H3K36me2/3 in vitro with a higher binding affinity towards H3K36me2, which is abrogated by overgrowth syndrome-derived missense mutations. Taken together, our study uncovers a trans-chromatin regulatory pathway that, when perturbed, promotes neoplastic and developmental overgrowth.
2019-08-30 | GSE118785 | GEO
Project description:Bulk RNA sequencing of small intestinal organoids obtained from germline Tifa-/- versus wild-type littermate control mice stimulated in vitro with IL-22 or IL-22 plus ADP-heptose versus mock control
2025-05-01 | E-MTAB-14831 | biostudies-arrayexpress
Project description:Genetic mutations are being thoroughly mapped in human cancers, yet a fundamental question in cancer biology is whether such mutations are functionally required for cancer initiation, maintenance of established cancer, or both. Here, we study this question in the context of human acute myeloid leukemia (AML), where DNMT3A:R882 missense mutations often arise early, in pre-leukemic clonal hematopoiesis, and corrupt the DNA methylation landscape to initiate leukemia. We developed CRISPR-based methods to directly correct DNMT3A:R882 mutations in leukemic cells obtained from patients. Surprisingly, DNMT3A:R882 mutations were largely dispensable for disease maintenance. Replacing DNMT3A:R882 mutants with wild-type DNMT3A did not impair the ability of AML cells to engraft in vivo, and minimally altered DNA methylation. Taken together, DNMT3A:R882 mutations are initially necessary for AML initiation, but are largely dispensable for disease maintenance. The notion that initiating oncogenes differ from those that maintain cancer has important implications for cancer evolution and therapy.
2025-10-27 | GSE308272 | GEO
Project description:Genetic mutations are being thoroughly mapped in human cancers, yet a fundamental question in cancer biology is whether such mutations are functionally required for cancer initiation, maintenance of established cancer, or both. Here, we study this question in the context of human acute myeloid leukemia (AML), where DNMT3A:R882 missense mutations often arise early, in pre-leukemic clonal hematopoiesis, and corrupt the DNA methylation landscape to initiate leukemia. We developed CRISPR-based methods to directly correct DNMT3A:R882 mutations in leukemic cells obtained from patients. Surprisingly, DNMT3A:R882 mutations were largely dispensable for disease maintenance. Replacing DNMT3A:R882 mutants with wild-type DNMT3A did not impair the ability of AML cells to engraft in vivo, and minimally altered DNA methylation. Taken together, DNMT3A:R882 mutations are initially necessary for AML initiation, but are largely dispensable for disease maintenance. The notion that initiating oncogenes differ from those that maintain cancer has important implications for cancer evolution and therapy.
2025-10-27 | GSE308271 | GEO
Project description:The transcriptome of 8 strains were studied during 7 stages of the Morphological phases of sporulation P0 = Resuspention of cells in sporulation medium; P1 = Onset of sporulation before asymmetric division; P2 = Visible asymmetric septum; P3 = Ongoing engulfment of the forespore compartment by the mother cell compartment of sporulating cells; P4 = Completed engulfment (engulfed phase-dark forespores are surrounded by the mother-cell cytoplasm); P5 = Maturation (ongoing dehydration of the forespore core seen as a transition of phase-dark forespores into phase-bright foresppores); P6 = Phase-bright forespores (sporulation almost completed, mother-cells contain phase-bright dehydrated forespores).
2018-03-08 | GSE108659 | GEO