Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PSPC1 selectively controls tumorigenesis and oncogenic transcription in acute myeloid leukemia [RNA-seq]

ABSTRACT: Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy characterized by the blockage of myeloid cell differentiation and uncontrolled proliferation of immature myeloid cells. Here, we show that paraspeckle component 1 (PSPC1) is aberrantly overexpressed in AML and high level of PSPC1 expression is associated with poor survival in AML patients. We demonstrate that PSPC1 loss dramatically suppresses leukemia maintenance and initiation/development as well as self-renewal of leukemia stem cells (LSCs) but has no effect on normal hematopoiesis. Mechanistically, PSPC1 interacts with PU.1, and they co-occupy the chromatin, especially at promoter regions proximal to transcription start site (TSS). Recruitment of PSPC1 and PU.1 on co-bound regions was dependent on each other to regulate target genes expression such as NDC1, a prognostic marker in multiple tumors. Collectively, our findings uncover a selective and crucial role of PSPC1 in AML and highlight its potential as a promising therapeutic target for myeloid malignancies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE247301 | GEO | 2025/05/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PSPC1 selectively controls tumorigenesis and oncogenic transcription in acute myeloid leukemia [ChIP-seq]

Project description:Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy characterized by the blockage of myeloid cell differentiation and uncontrolled proliferation of immature myeloid cells. Here, we show that paraspeckle component 1 (PSPC1) is aberrantly overexpressed in AML and high level of PSPC1 expression is associated with poor survival in AML patients. We demonstrate that PSPC1 loss dramatically suppresses leukemia maintenance and initiation/development as well as self-renewal of leukemia stem cells (LSCs) but has no effect on normal hematopoiesis. Mechanistically, PSPC1 interacts with PU.1, and they co-occupy the chromatin, especially at promoter regions proximal to transcription start site (TSS). Recruitment of PSPC1 and PU.1 on co-bound regions was dependent on each other to regulate target genes expression such as NDC1, a prognostic marker in multiple tumors. Collectively, our findings uncover a selective and crucial role of PSPC1 in AML and highlight its potential as a promising therapeutic target for myeloid malignancies.

2025-05-30 | GSE247300 | GEO

A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency [RNA-seq]

Project description:The mammalian Ten-eleven translocation (TET) family proteins regulate the epigenome through catalytic activity (CA)-dependent and -independent functions. While catalytic activity of TETs has been intensely studied as DNA demethylation enzymes, little is known about their CA-independent function in early embryo development. Here we defined the CA-independent function of TET1 in naïve-to-formative pluripotent states transition. Using a proteomics method, we mapped the TET1 interactome and identified Paraspeckle component 1 (PSPC1) as a partner of TET1 for transcriptional repression at the bivalent genes in early development. Genome-wide location analysis revealed that PSPC1-bound regions largely overlap with TET1 and Polycomb repressive complex 2 (PRC2) subunits. Functional studies with genetic methods indicated that PSPC1 and TET1 repress, while lncRNA Neat1 activates the bivalent genes during their transcriptional activation. In embryonic stem cell (ESC) state, Neat1 tethers TET1, PSPC1, and PRC2 at promoters. During the ESCs to formative Epiblast like stem cells (EpiLCs) differentiation, PSPC1 and TET1 repress the PRC2 affinity to nascent mRNA transcripts of bivalent genes, while Neat1 facilitates PRC2 binding to those transcripts. Our study reveals a molecular mechanism by which proteins TET1 and PSPC1, and lncRNA Neat1 dynamically regulate gene transcription by modulating the PRC2 activity in pluripotent states transition.

2022-06-07 | GSE182441 | GEO

A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency [ChIRP-Seq]

2022-06-07 | GSE199265 | GEO

A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency [ChIP-seq]

2022-06-07 | GSE182442 | GEO

A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency [H3 ChIP-Seq]

2022-06-07 | GSE199266 | GEO

Activation of Wnt/β-catenin Signaling Blocks Monocyte-Macrophage Differentiation Through Antagonizing PU.1-Targeted Gene Transcription

Project description:We have shown that β-catenin overexpression induced blockage of monocyte-macrophage differentiation by inhibiting PU.1-targeted gene transcription including Egr2 expression in myeloid progenitor cells. Our results suggest that compromised PU.1-targeted gene transcription induced by β-catenin overexpression, at least partially, may mediate a pathogenic role of β-catenin in myeloid leukemia.

2016-04-06 | GSE79932 | GEO

PSPC1 selectively controls tumorigenesis and oncogenic transcription in acute myeloid leukemia

Project description:PSPC1 selectively controls tumorigenesis and oncogenic transcription in acute myeloid leukemia

| PRJNA1037071 | ENA

Activation of Wnt/Î²-catenin Signaling Blocks Monocyte-Macrophage Differentiation Through Antagonizing PU.1-Targeted Gene Transcription

Project description:We have shown that Î²-catenin overexpression induced blockage of monocyte-macrophage differentiation by inhibiting PU.1-targeted gene transcription including Egr2 expression in myeloid progenitor cells. Our results suggest that compromised PU.1-targeted gene transcription induced by Î²-catenin overexpression, at least partially, may mediate a pathogenic role of Î²-catenin in myeloid leukemia. PUER cells were infected with retrovirus expressing beta-catenin-S33Y or control vector MIGR1. Five days after infection, the GFP positive cells were sorted by flow cytometry, and were treated with 4-OHT to induce the expression of PU.1. Total RNA was exacted from cell samples and purified by RNeasy Micro kit (Qiagen). cRNAs were generated and hybridized to the mouse whole genome 4Ã44K arrays according to manufacturerâs instructions (Agilent Technologies).

2016-04-06 | E-GEOD-79932 | biostudies-arrayexpress

The synergistic effect of c-Myb hyperactivation and Pu.1 deficiency in inducing Pelger-Huët anomaly and promoting sAML transformation

Project description:Patients with acute myeloid leukemia developed from myelodysplastic syndrome (MDS/AML) have poor prognosis with more complex genetic mutations. Genomic analyses have shown complex association among mutant genes, including co-occurring and mutually exclusive. It has been reported that hyperactivation of MYB or deficiency of PU.1 could induce myeloid preleukemia. The simultaneous abnormal expression of these two proteins has been documented in some AML patients. However, the association of MYB and PU.1 in the pathogenesis of malignant hematopoiesis remains unclear. In this study, we used the c-Myb-hyperactivation and Pu.1-deficient double-strain (c-mybhyper;pu.1G242D/G242D) zebrafish to clarify the synergistic role of c-Myb and Pu.1 in promoting MDS/AML development. We found that the c-mybhyper;pu.1G242D/G242D mutant displayed excessive expansion and differentiation arrest of neutrophils, and progressed to MDS/AML with a high ratio. Interestingly, a group of poorly differentiated Pelger-Huët-like neutrophils was identified in c-mybhyper;pu.1G242D/G242D adulthood and might be associated with MDS/AML progression. Moreover, treated the c-mybhyper;pu.1G242D/G242D zebrafish with a combination of the cell cycle inhibitor cytarabine (Ara-C) and the differential inducer all-trans retinoic acid (ATRA) could effectively relieve the leukemic symptoms. Our findings revealed that c-Myb hyperactivation and Pu.1 deficiency synergistically induced MDS/AML. Furthermore, c-mybhyper;pu.1G242D/G242D zebrafish might serve as a suitable MDS/AML model for drug screening.

2025-03-19 | GSE206979 | GEO

Expression data from PU.1low URE-/- AML cell line after treatment with small molecule acting as PU.1 inhibitor

Project description:Downregulation of the hematopoietic transcription factor PU.1 in PU.1 low acute myeloid leukemia cells (AML) by novel heterocyclic diamidines or PU.1 inhibitors leads to decrease cell proliferation and apoptosis, representing a new therapeutic strategy for AML treatment. These inhibitors induces decreased PU.1 binding on its target sites, as well as deregulation in PU.1 canonical target genes We used microarray to identify the pathways deregulated after drug treatment.

2017-12-07 | GSE77651 | GEO

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