التفاصيل البيبلوغرافية
| العنوان: |
Table_2_Depletion of tet2 results in age-dependent changes in DNA methylation and gene expression in a zebrafish model of myelodysplastic syndrome.xlsx |
| المؤلفون: |
Yaseswini Neelamraju, Evisa Gjini, Sagar Chhangawala, Hao Fan, Shuning He, Chang-Bin Jing, Ashley T. Nguyen, Subhash Prajapati, Caroline Sheridan, Yariv Houvras, Ari Melnick, A. Thomas Look, Francine E. Garrett-Bakelman |
| سنة النشر: |
2023 |
| المجموعة: |
Frontiers: Figshare |
| مصطلحات موضوعية: |
Hematology, Stem Cells, Cancer Therapy (excl. Chemotherapy and Radiation Therapy), Haematological Tumours, Genetic Immunology, TET2, myelodysplastic syndrome, hematopoietic progenitors, zebrafish, DNA methylation |
| الوصف: |
Introduction Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, cytopenias, and dysplasia. The gene encoding ten-eleven translocation 2 (tet2), a dioxygenase enzyme that catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine, is a recurrently mutated tumor suppressor gene in MDS and other myeloid malignancies. Previously, we reported a stable zebrafish line with a loss-of-function mutation in the tet2 gene. The tet2 m/m -mutant zebrafish developed a pre-MDS state with kidney marrow dysplasia, but normal circulating blood counts by 11 months of age and accompanying anemia, signifying the onset of MDS, by 24 months of age. Methods In the current study, we collected progenitor cells from the kidney marrows of the adult tet2 m/m and tet2 wt/wt fish at 4 and 15 months of age and conducted enhanced reduced representation of bisulfite sequencing (ERRBS) and bulk RNA-seq to measure changes in DNA methylation and gene expression of hematopoietic stem and progenitor cells (HSPCs). Results and discussion A global increase in DNA methylation of gene promoter regions and CpG islands was observed in tet2 m/m HSPCs at 4 months of age when compared with the wild type. Furthermore, hypermethylated genes were significantly enriched for targets of SUZ12 and the metal-response-element-binding transcription factor 2 (MTF2)—involved in the polycomb repressive complex 2 (PRC2). However, between 4 and 15 months of age, we observed a paradoxical global decrease in DNA methylation in tet2 m/m HSPCs. Gene expression analyses identified upregulation of genes associated with mTORC1 signaling and interferon gamma and alpha responses in tet2 m/m HSPCs at 4 months of age when compared with the wild type. Downregulated genes in HSPCs of tet2-mutant fish at 4 months of age were enriched for cell cycle regulation, heme metabolism, and interleukin 2 (IL2)/signal transducer and activator of transcription 5 (STAT5) signaling, possibly related to ... |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Table_2_Depletion_of_tet2_results_in_age-dependent_changes_in_DNA_methylation_and_gene_expression_in_a_zebrafish_model_of_myelodysplastic_syndrome_xlsx/24139743 |
| DOI: |
10.3389/frhem.2023.1235170.s003 |
| الاتاحة: |
https://doi.org/10.3389/frhem.2023.1235170.s003
https://figshare.com/articles/dataset/Table_2_Depletion_of_tet2_results_in_age-dependent_changes_in_DNA_methylation_and_gene_expression_in_a_zebrafish_model_of_myelodysplastic_syndrome_xlsx/24139743 |
| Rights: |
CC BY 4.0 |
| رقم الانضمام: |
edsbas.85A45AA0 |
| قاعدة البيانات: |
BASE |