Ontology highlight
ABSTRACT:
PROVIDER: PRJNA412416 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6109250_1.fastq.gz | Fastqsanger.gz | |||
| SRR6109250_2.fastq.gz | Fastqsanger.gz | |||
| SRR6109260_1.fastq.gz | Fastqsanger.gz | |||
| SRR6109260_2.fastq.gz | Fastqsanger.gz | |||
| SRR6109270_1.fastq.gz | Fastqsanger.gz |
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Project description:NGS of DS CRISPR-Cas-deleted MTBC and one DS and one MDR T3_Eth
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Project description:Down syndrome (DS) is the most common genetic condition that causes intellectual disability in humans. The molecular mechanisms behind the DS phenotype remain unclear. Therefore, in the present study, induced pluripotent stem cells (iPSCs) from a patient with DS and a normal control (NC) patient were differentiated into iPSCs‐derived neural stem cells (NSCs). Single-cell RNA sequencing was performed to achieve a comprehensive single-cell level differentiation roadmap for DS-iPSCs. The results demonstrated that iPSCs can differentiate into NSCs in both DS and NC samples. Furthermore, 19,422 cells were obtained from iPSC samples (8,500 cells for DS and 10,922 cells for the NC) and 16,506 cells from NSC samples (7,182 cells for DS and 9,324 cells for the NC), which had differentiated from the iPSCs. A cluster of DS-iPSCs, named DS-iPSCs-not differentiated (DSi-PSCs-ND), which had abnormal expression patterns compared with NC-iPSCs, were demonstrated to be unable to differentiate into DS-NSCs. Further analysis of the differentially expressed genes revealed that inhibitor of differentiation family members, which exhibited abnormal expression patterns throughout the differentiation process from DS-iPSCs to DS-NSCs, may potentially have contributed to the neural differentiation of DS-iPSCs. Moreover, abnormal differentiation fate was observed in DS-NSCs, which resulted in the increased differentiation of glial cells, such as astrocytes, but decreased differentiation into neuronal cells. Furthermore, functional analysis demonstrated that DS-NSCs and DS-NPCs had disorders in axon and visual system development. Biological experiments were also performed to validate these results and the present study provided a new insight into the pathogenesis of DS.
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Project description:Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples
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Project description:A validation experiment performed on HEK293 cell lines after genome editing. The design contains three duplicate runs consisted of: HEK293 wild type cell line HEK293 with MIR484 gene knockdown using CRISPR-Cas9 HEK293 with MIR185 gene knockout using CRISPR-Cas9
2023-06-16 | E-MTAB-13009 | biostudies-arrayexpress
Project description:Children with Down syndrome (DS) are at high risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia (DS-AMKL). GATA1 gene mutations are detected in almost all TAM and DS-AMKL samples, leading to exclusive expression of short GATA1 protein (GATA1s) lacking of N-terminal domain (NTD). However, it remains to be clarified how GATA1s is involved with both disorders. To investigate how the loss of GATA1 NTD is involved in the molecular mechanisms of leukemogenesis in DS, we established the K562 GATA1s (K562-G1s) clones expressing only GATA1s by CRISPR/Cas9 genome editing. The K562-G1s clones expressed KIT at higher levels compared to the wild type K562 (K562-WT). With Chromatin-Immunoprecipitation (ChIP) studies, we found that both GATA1 and GATA1s were bound upstream of the KIT gene. To understand the status of the KIT gene in K562-WT and one of K562-G1 subclone, C1 #26, we also performed ChIP-seq of histone modifications. Although the ChIP-seq signals of C1 #26 tended to be slightly lower than those of K562-WT, the activation status of the KIT gene demonstrated by the histone modifications was not significantly different between K562-WT and C1#26. Chromosome conformation capture (3C)-modified proximity assays revealed the difference in the conformation of the KIT gene between the K562-WT and C1 #26. We found that the lack of the NTD of GATA1 altered the genomic structure of the KIT gene, resulting in dysregulation of KIT expression. These results suggest that the NTD of GATA1 is essential for proper genomic conformation and gene expression regulation of the KIT gene and that perturbation of this mechanism might be involved in the pathogenesis of TAM and DS-AMKL.
2022-11-29 | GSE159072 | GEO
Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples.
2010-08-01 | GSE16677 | GEO
Project description:Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.
2016-06-17 | GSE83449 | GEO
Project description:As part of a clinical trial of the MDM2 inhibitor DS-3032b, 41 primary tumor samples were obtained before treatment from 38 patients newly diagnosed with AML, or relapsed or refractory to standard induction chemotherapy Gene expression features of pretreatment samples, along with TP53 mutation status, were found to correlate with clinical response to DS-3032b (manuscript under review).
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Project description:Aneuploidy and structural aberrations affecting chromosome 21 (Hsa21) are the most frequent in cytogentic events in acute myeloid leukemia. However, it remains unclear why leukemic blasts select for amplifications of Hsa21 or parts of it and why children with Down syndrome (i.e. trisomy 21) are at a high risk of developing leukemia. Here, we propose that disequilibrium of the RUNX1 isoforms and resultant RUNX1A dominance are key to trisomy 21-associated leukemogenesis. Using a Hsa21-focussed CRISPR-Cas9 screen, we uncovered a strong and specific RUNX1 dependency in myeloid leukemia associated with Down syndrome (ML-DS). High levels of RUNX1A – as seen in ML-DS – synergized with the pathognomonic Gata1s mutation in ML-DS pathogenesis, an effect that was reversed upon restoration of the normal RUNX1A:RUNX1C equilibrium. Mechanistically, RUNX1A displaces RUNX1C from its endogenous binding sites and recruits the MYC cofactor MAX to induce oncogenic programs and perturb normal differentiation. This presents a therapeutic vulnerability that can be exploited by interfering with MYC:MAX dimerization. Our study highlights the importance of alternative splicing in leukemogenesis, and paves the way for developing specific and targeted therapies for ML-DS as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.
2023-05-10 | PXD030616 | Pride