Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9140130.fastq.gz | Fastqsanger.gz | |||
| SRR9140140.fastq.gz | Fastqsanger.gz | |||
| SRR9140150.fastq.gz | Fastqsanger.gz | |||
| SRR9140131.fastq.gz | Fastqsanger.gz | |||
| SRR9140141.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 27 |
Similar Datasets
Project description:Senescence, a stable state of growth arrest, affects many physiological and pathophysiological processes, especially aging. Previous work has indicated that transcription factors (TFs) play a role in regulating senescence. However, a systematic study of regulatory TFs during replicative senescence (RS) using multi-omics analysis is still lacking. Here, we generated time-resolved RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets during RS of mouse skin fibroblasts, which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and epigenome. Through integrative analysis and genetic manipulation, we found that transcription factors E2F4, TEAD1 and AP-1 are key regulators of RS. Overexpression of E2f4 improved cellular proliferative capacity, attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites (DMSs). Moreover, knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated transcriptome. In addition, knockdown of Atf3, one member of AP-1 superfamily TFs, reduced Cdkn2a (P16) expression in pre-senescent fibroblasts. Taken together, results of this study identified transcription factors regulating the senescence program through multi-omics analysis, providing potential therapeutic targets for anti-aging.
2021-10-08 | GSE185416 | GEO
Project description:Ringsideroblasts(RS) emerge as result of aberrant erythroid differentiation leading to excessive mitochondrial iron accumulation. This feature is characteristic for myelodysplastic syndromes with mutations in spliceosome gene SF3B1. However, RS can also be observed in patients diagnosed with acute myeloid leukemia (AML). The objective of this study was to characterize the presence of RS in a cohort of 109 AML and 17 high-risk MDS patients. Clinically, RS-AML is enriched for ELN adverse-risk (55%). In line with this finding, 35% of all cases had complex cytogenetic aberrancies and TP53 was most recurrently mutated in this cohort (42%), followed by DNMT3A (29%), RUNX1 (21%) and ASXL1 (19%). In contrast to RS-MDS, the incidence of SF3B1 mutations was low (8%). Whole exome sequencing and SNP array analysis on a subset of patients did not uncover one single defect underlying the RS phenotype. Shared genetic defects between erythroblasts and total mononuclear cell fraction indicate common ancestry for the erythroid lineage and the myeloid blast cells in RS-AML patients. Gene expression analysis by performing RNA sequencing on CD34+ AML cells revealed differential gene expression between RS-AML and a separate AML cohort, including genes involved in megakaryocytic/erythroid differentiation and mRNA splicing. Furthermore, several heme-metabolism-related genes were found upregulated in RS-AML, as was observed in SF3B1mut MDS. These results demonstrate that erythroblasts share ancestry with malignant myeloid blast cells in RS-AML. The genetic background of RS-AML differs from that of RS-MDS, however downstream effector pathways may be comparable, providing a possible explanation for presence of RS in AML.
2020-03-17 | GSE127861 | GEO
Project description:Primary alveolar type II cells were either treated with vehicle or NaHS for 6 h and 24 h (RS-266 samples). Primary alveolar type II cells treated with GYY4137 at 100 µM concentration were exposed to either 21% O2 or 85% O2 for 24 h (RS-284 samples). Overall no changes in gene expressionwere found in the corrected p values of both microarray studies.
2014-05-20 | GSE53030 | GEO
Project description:SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and affects the elderly population. Here, using single-cell technologies and functional validation studies of primary SF3B1-mutant MDS-RS samples (MDS-RS-3-bis, MDS-RS-13, and MDS-RS-14), we show that SF3B1 mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of EIF2AK1 inhibitors to overcome transfusion dependency in patients with SF3B1-mutant MDS-RS with impaired red blood cell production. MACS-purified CD34+ cells were subjected to a 3-phase in vitro culture as described previously (Huang et al., 2020a). Cells were maintained in phase 1 from the day of collection until day 8, at which time the cells underwent ribonucleoprotein-based gene editing and were transitioned to phase 2 medium. On day 13 of culture, the cells were transitioned to phase 3 medium. Samples for Western blot and cytospin analyses, and sample for flow cytometry were harvested on day 13 or 15 of culture, respectively.
2022-07-19 | GSE202722 | GEO
Project description:Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). While RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the pre-existing CLL, mechanisms leading to RS have not been clarified yet. To better understand the pathogenesis of RS, we analyzed a series of cases including: 59 RS, 28 CLL-phase of RS, 315 CLL and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL-phase, being present in approximately half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. While RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL-phase preceding RS had not a generalized increase in genomic complexity when compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
2013-09-20 | GSE50252 | GEO
Project description:Since oncogenes induce DNA replication stress (RS), cancer cells rely on the intra S-phase checkpoint for survival. Consequently, RS inducing drugs and ATR and CHK1 inhibitors are exploited as anti-cancer therapy. However, drug resistance limits efficient use. This raises the question what determines sensitivity of individual cancer cells to RS. Here, we report that oncogenic RAS dampens the P53 checkpoint which confers sensitivity to RS. We demonstrate that inducible expression of HRASG12V leads to mild RS in RPE-hTERT cells and was sufficient to sensitize cells to ATR and CHK1 inhibitors. Using RNA-sequencing we discovered that P53 signaling is essential for the response to RS. However, oncogenic RAS attenuates transcription of P53 and its target genes. Accordingly, live cell imaging shows that HRASG12V exacerbates RS in S/G2-phase. Thus, our results suggest that hyperactivation of the MAPK pathway could predict durable responses to RS inducing drugs in cancer patients
2022-04-05 | GSE168987 | GEO
Project description:Cellulosimicrobium sp. RS strain:RS Genome sequencing
| PRJNA1186700 | ENA
Project description:ralstonia solanacearum Rs strain:Rs Genome sequencing
| PRJNA221562 | ENA
Project description:Pediococcus pentosaceus strain:RS-1 | isolate:Plant samples Genome sequencing
| PRJNA1134429 | ENA