Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expanding the transcriptomic sequence space in leukaemia by RUNX1/RUNX1T1-mediated alternative splicing

ABSTRACT: Expanding the transcriptomic sequence space in leukaemia by RUNX1/RUNX1T1-mediated alternative splicing

PROVIDER: PRJNA674515 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12978648_1.fastq.gz	Fastqsanger.gz
	SRR12978648_2.fastq.gz	Fastqsanger.gz
	SRR12978649_1.fastq.gz	Fastqsanger.gz
	SRR12978649_2.fastq.gz	Fastqsanger.gz
	SRR12978650_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Expanding the transcriptomic sequence space in leukaemia by RUNX1/RUNX1T1-mediated alternative splicing

Project description:The fusion oncogene RUNX1/RUNX1T1 encodes an aberrant transcription factor, which plays a key role in the initiation and maintenance of acute myeloid leukaemia. In this study we comprehensively identify and characterize splicing events associated with RUNX1/RUNX1T1. We show that this oncogene is a regulator of the alternative RNA splicing in leukaemic cells. We found two principal mechanisms underlying changes in the production of RNA isoforms: (i) RUNX1/RUNX1T1-mediated regulation of alternative transcription start sites selection, and (ii) direct or indirect control of the expression of the genes encoding splicing factors. The first mechanism leads to the expression of RNA isoforms with alternative structure of the 5’-UTR regions. The second mechanism generates alternative transcripts with new junctions between internal cassettes and constitutive exons. We also show that RUNX1/RUNX1T1-mediated differential splicing affects several functional groups of genes and produces proteins with unique conserved domain structures. In summary, this study reveals a novel layer of transcriptome re-organization in leukaemia by an aberrant transcriptional regulator.

2020-11-05 | GSE160792 | GEO

Single-cell RNA sequencing of RUNX1-RUNX1T1(9a) transformed mouse bone marrow cells

Project description:Single-cell RNA sequencing analysis of RUNX1-RUNX1T1(9a) transformed c-kit positive cells with (Kat2a WT) and without Kat2a (Kat2a NULL). Lineage negative bone marrow cells were collected from Kat2a fl/fl Mx1-Cre-/- and Kat2a fl/fl Mx1-Cre +/- animals after pIpC treatment and transduced with RUNX1-RUNX1T1(9a) expressing retrovirus (reported by GFP expression). Cells were injected into irradiated C57BL6 mice and GFP positive c-Kit positive bone marrow cells collected 2 and 4 months after transplantation. Cells were processed for single-cell RNA sequencing library preparation (10X chromium single cell) and next gene sequencing following 10X genomics v2 protocol.

2022-08-24 | E-MTAB-10853 | biostudies-arrayexpress

Functional Characterization of Cooperating MGA Mutations in RUNX1::RUNX1T1 Acute Myeloid Leukemia [RNA-seq]

Project description:MGA (Max-gene associated) is a dual-specificity transcription factor that negatively regulates MYC-target genes to inhibit proliferation and promote differentiation. Loss-of-function mutations in MGA have been commonly identified in several hematological neoplasms, including acute myeloid leukemia (AML) with RUNX1::RUNX1T1, however, very little is known about the impact of these MGA alterations on normal hematopoiesis or disease progression. We show that representative MGA mutations identified in patient samples abolish protein-protein interactions and transcriptional activity. Using a series of human and mouse model systems, including a newly developed conditional knock-out mouse strain, we demonstrate that loss of MGA results in upregulation of MYC and E2F targets, cell cycle genes, mTOR signaling, and oxidative phosphorylation in normal hematopoietic cells, leading to enhanced proliferation. The loss of MGA induces an open chromatin state at promotors of genes involved in cell cycle and proliferation. RUNX1::RUNX1T1 expression in Mga-deficient murine hematopoietic cells leads to a more aggressive AML with a significantly shortened latency. These data show that MGA regulates multiple pro-proliferative pathways in hematopoietic cells and cooperates with the RUNX1::RUNX1T1 fusion oncoprotein to enhance leukemogenesis.

2024-05-15 | GSE253748 | GEO

Functional Characterization of Cooperating MGA Mutations in RUNX1::RUNX1T1 Acute Myeloid Leukemia [ATAC-seq]

2024-05-15 | GSE253752 | GEO

Functional Characterization of Cooperating MGA Mutations in RUNX1::RUNX1T1 Acute Myeloid Leukemia [Cut&Run]

2024-05-15 | GSE253750 | GEO

ZBTB7A prevents RUNX1-RUNX1T1 dependent clonal expansion of human hematopoietic progenitor cells

Project description:ZBTB7A is frequently mutated in acute myeloid leukemia (AML) with t(8;21) translocation. However, the oncogenic collaboration between mutated ZBTB7A and the RUNX1-RUNX1T1 fusion gene in AML t(8;21) remains unclear. Here, we investigate the role of ZBTB7A and its mutations in the context of normal and malignant hematopoiesis.

2020-04-07 | GSE140472 | GEO

ChIP-seq for RUNX1 and ETV6-RUNX1 in an induced pluripotent stem cell model of ETV6-RUNX1 pre-leukaemia

Project description:ETV6-RUNX1 is a first-hit mutation in childhood B cell precursor acute lymphoblastic leukaemia. ETV6-RUNX1 is a fusion protein which inherits the DNA-binding runt domain from RUNX1. Here we performed chromatin precipitation for native RUNX1 and ETV6-RUNX1 using RUNX1 antibodies and specifically for the ETV6-RUNX1 fusion using a V5-tag pull down.

2022-10-31 | E-MTAB-12208 | biostudies-arrayexpress

The Distinct Profile of Tumor-Reactive T Cells in RUNX1::RUNX1T1 AML Bone Marrow Unveiled by Single-Cell Analysis

Project description:Unlike the well-known knowledge of tumor-infiltrating T cells in solid tumors, the overall T cell state and the characteristics of tumor-reactive T cells in RUNX1:RUNX1T1 acute myeloid leukemia remain unclear. In this study, we employed single-cell transcriptome sequencing and single-cell TCR sequencing to elucidate the characteristics of T cells in the bone marrow of RUNX1:RUNX1T1 leukemia patients. Both CD4+ and CD8+ T cells exhibited features of reduced immune reserves and an increase in terminally differentiated T cells, indicative of immune mobilization.

2024-10-08 | GSE263099 | GEO

CSF3R T618I collaborates with RUNX1-RUNX1T1 to expand hematopoietic progenitors and sensitizes to GLI-inhibition

Project description:Activating CSF3R mutations are recurrent in AML with t(8;21) translocation. However, the nature of oncogenic collaboration between alterations of CSF3R and the t(8;21) associated RUNX1-RUNX1T1 fusion remains unclear. In CD34+ hematopoietic stem and progenitor cells from healthy donors, double oncogene expression led to a clonal advantage, increased self-renewal potential, as well as blast-like morphology and distinct immunophenotype. Gene expression profiling revealed hedgehog-signaling as a potential mechanism, with upregulation of GLI2 constituting a putative pharmacological target. Both primary hematopoietic cells and the t(8;21) positive AML cell line SKNO-1 showed increased sensitivity to the GLI-inhibitor GANT61 when expressing CSF3R T618I. Our findings suggest that during leukemogenesis the RUNX1-RUNXT1 fusion and CSF3R mutation act in a synergistic manner to alter hedgehog signaling which can be exploited therapeutically.

2023-10-18 | GSE230755 | GEO

Transcription profiling of human normal progenitor cells mutated for RUNX1-RUNX1 during myeloid and erythroid development to identify genes disregulated by RUNX1-RUNX1

Project description:In order to identify genes dysregulated by the aberrant transcriptional activity of RUNX1-RUNX1T1, we used microarrays to determine the effect of this mutation on gene expression during myeloid and erythroid development of normal human progenitor cells.

2007-10-01 | E-MEXP-583 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data