Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RBM5 is essential for the maintenance of leukemia stem cells by regulating a leukemic transcription program in cooperation with MYC [bulk RNA-seq]

ABSTRACT: Acute myeloid leukemia (AML) represents a type of malignant hematological disease that is caused by the dysregulated developmental program of leukemia stem cells (LSCs). RBM5 was recently reported as a key regulator in maintaining the survival of human leukemia cells via non-canonical transcriptional activation of HOXA9. However, its function in LSCs and the broad genome-wide transcriptional targets remain elusive. Here, we report that RBM5 is required for murine leukemogenesis and maintains self-renewal of LSCs in vivo, but dispensable for normal hematopoiesis. RBM5 is highly expressed in LSCs, and its deficiency results in specifically defective LSC function with the inhibition of self-renewal gene expression and induction of myeloid differentiation program. Gene expression, chromatin accessibility, and direct genome-wide RBM5 binding further identify the direct transcriptional targets of RBM5 in primary leukemia cells including several stemness genes Hoxa9 and Myc. Forced expression of both HOXA9 and MYC rescued the RBM5 depletion effects on colony formation and self-renewal gene expression program. Thus, our study shows that RBM5 regulates the AML LSC program through transcriptional regulation and provides a rationale to therapeutically target RBM5 in myeloid leukemia.

ORGANISM(S): Mus musculus

PROVIDER: GSE301020 | GEO | 2026/06/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RBM5 is essential for the maintenance of leukemia stem cells by regulating a leukemic transcription program in cooperation with MYC [scRNA-seq]

Project description:Acute myeloid leukemia (AML) represents a type of malignant hematological disease that is caused by the dysregulated developmental program of leukemia stem cells (LSCs). RBM5 was recently reported as a key regulator in maintaining the survival of human leukemia cells via non-canonical transcriptional activation of HOXA9. However, its function in LSCs and the broad genome-wide transcriptional targets remain elusive. Here, we report that RBM5 is required for murine leukemogenesis and maintains self-renewal of LSCs in vivo, but dispensable for normal hematopoiesis. RBM5 is highly expressed in LSCs, and its deficiency results in specifically defective LSC function with the inhibition of self-renewal gene expression and induction of myeloid differentiation program. Gene expression, chromatin accessibility, and direct genome-wide RBM5 binding further identify the direct transcriptional targets of RBM5 in primary leukemia cells including several stemness genes Hoxa9 and Myc. Forced expression of both HOXA9 and MYC rescued the RBM5 depletion effects on colony formation and self-renewal gene expression program. Thus, our study shows that RBM5 regulates the AML LSC program through transcriptional regulation and provides a rationale to therapeutically target RBM5 in myeloid leukemia.

2026-06-08 | GSE301116 | GEO

Rbm5 is required for sustaining leukemia stem cells by modulating a leukemic transcriptional program in concert with the Myc network [ChIP-Seq]

Project description:Acute myeloid leukemia (AML) represents a type of malignant hematological disease that is caused by the dysregulated developmental program of leukemia stem cells (LSCs). Compared to other hematological malignancies, AML often predicts poor prognosis and unfavorable treatment outcomes in the clinic, urging the need for complex mechanism studies. Rbm5 was recently reported as a key regulator in maintaining the survival of human AML cell lines via non-canonical transcriptional activation of Hoxa9. However, its function in LSCs and the broad genome-wide transcriptional targets remain elusive. Here, using genetic mouse models, ex vivo AML culture, and patient-derived xenografts, we report that Rbm5 is required for murine leukemogenesis and maintains self-renewal of LSCs in vivo but is dispensable for normal hematopoiesis. Rbm5 is highly expressed in LSCs, and its deficiency results in specifically defective LSC function, along with the inhibition of self-renewal gene expression and the induction of a myeloid differentiation program. Multi-disciplinary mechanistic investigations targeting gene expression at both the single-cell level and in bulk populations, together with an acute RBM5 degradation system, further identified the direct transcriptional targets of Rbm5 in primary leukemia cells, including stemness genes, such as Hoxa9 and Myc. Moreover, RBM5 not only interacts with MYC but also maintains its protein levels, thereby sustaining the Myc downstream transcriptional network through its proper genome-wide occupancy. Forced expression of Myc sufficiently rescued the Rbm5-depleted defects both in vitro and in vivo. Thus, our study demonstrates that Rbm5 regulates the AML LSC program through non-canonical transcriptional mechanisms, providing a strong rationale for therapeutically targeting Rbm5 in the treatment of myeloid leukemia.

2026-06-08 | GSE307072 | GEO

Msi2 sustains the MLL leukemia stem cell regulatory program

Project description:Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Genetic and epigenetic alterations cause a dysregulated developmental program in leukemia. The MSI2 RNA binding protein has been previously shown to predict poor survival in leukemia. We demonstrate that the conditional deletion of Msi2 results in delayed leukemogenesis, reduced disease burden and a loss of LSC function. Gene expression profiling of the Msi2 ablated LSCs demonstrates a loss of the HSC/LSC and an increase in the differentiation program. The gene signature from the Msi2 deleted LSCs correlates with survival in AML patients. MSI2’s maintains the MLL self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc and Ikzf2. We further demonstrate that shRNA depletion of the MLL target gene Ikzf2 also contributes to MLL leukemia cell survival. Our data provides evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and a rationale for clinically targeting MSI2 in myeloid leukemia. RNA-Seq was performed on sorted c-Kit high leukemic cells from 2 Msi2 -/- and 2 Msi2 f/f mice.

2015-01-15 | E-GEOD-64545 | biostudies-arrayexpress

Msi2 sustains the MLL leukemia stem cell regulatory program

2015-01-15 | GSE64545 | GEO

Transcription profiling of mouse model of AML - hierarchical maintenance of MLL myeloid leukemia stem cells

Project description:Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells; The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. Experiment Overall Design: Refer to individual Series Experiment Overall Design: This SuperSeries is composed of the following subset Series: Experiment Overall Design: GSE13690: Gene expression profiling of murine MLL leukemias (whole BM) Experiment Overall Design: GSE13692: Expression profiling of MLL-AF10 myeloid leukemia cellular subsets Experiment Overall Design: GSE13693: Gene expression profiling of normal mouse myeloid cell populations

2009-02-21 | E-GEOD-13796 | biostudies-arrayexpress

Transcription profiling of mouse MLL leukemias (whole BM)

Project description:The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer. Experiment Overall Design: Samples are from five separate cohorts of mice where leukemia was initiated using distinct MLL fusion oncogenes: MLL-AF1p (n=9), MLL-AF10 (n=8), MLL-GAS7 (n=5), MLL-AF9 (n=5) and MLL-ENL (n=7). Four normal BM samples were also used as controls.

2009-02-21 | E-GEOD-13690 | biostudies-arrayexpress

miR-126 Governs Human Leukemia Stem Cell Quiescence and Therapeutic Resistance

Project description:In acute myeloid leukemia (AML), leukemia stem cells (LSC) play a central role in disease progression and recurrence due to their intrinsic capacity for self-renewal and chemotherapy resistance. Whereas epigenetic mechanisms balance normal blood stem cell self-renewal and fate decisions, mutation and dysregulation of epigenetic regulators are considered fundamental to leukemia initiation and progression. Alterations in miRNA function represent a non-canonical epigenetic mechanism influencing malignant hematopoiesis, however the function of miRNA in human LSC remains undetermined. Here we show that miRNA profiling of fractionated AML populations defines an LSC-specific signature that is highly prognostic for patient survival. Gain- and loss-of-function analyses demonstrated that miR-126 restrained cell cycle progression, prevented differentiation, and increased self-renewal of human LSC. By targeting the G0 to G1 gatekeeper CDK3, miR-126 preserved LSC quiescence and promoted chemotherapy resistance. Thus, in AML, miRNAs influence patient outcome through post-transcriptional regulation of stemness programs in LSC.

2016-03-31 | PXD001994 | Pride

Effect of RBM5 knockout or overexpression on transcription in MOLM13 AML cells

Project description:Background: The oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated. Results: Here, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription. Conclusions: We identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment. Keywords: Acute myeloid leukemia; CRISPR screen; Genome editing; HOXA9; RBM5.

2023-11-16 | GSE225633 | GEO

GADD45A loss enhances leukemia-initiating cell self-renewal and ferroptosis resistance in AML

Project description:Loss of GADD45A expression is implicated in poor patient outcomes in acute myeloid leukemia (AML) but its role in leukemia stem cells (LSCs) and disease pathogenesis remains largely unknown. Here we report that GADD45A loss is a critical determinant of high self-renewal potential and knockout of GADD45A supports long-term self-renewal and promotes LSC quiescence, accompanied by the acquisition of an increasingly aggressive phenotype upon serial transplantation in mice. The enhanced LSC characteristics are associated with GADD45A deletion-induced increase in key WNT/self-renewal-related genes. GADD45A knockout promotes engraftment of patient-derived xenograft (PDX) of relapsed AML in mice. Single cell RNA-seq on primary LSCs of AML PDXs and subsequent functional studies show that low expression of GADD45A, an important sensor of oxidative stress, confers ferroptosis resistance through upregulation of genes involved in detoxification of excess iron and reactive oxygen species (ROS), revealing a mechanism of drug resistance in primary AML with unfavorable cytogenetics.

2025-08-29 | E-MTAB-9803 | biostudies-arrayexpress

The H3K4-methyl epigenome regulates MLL leukemia stem cell oncogenic potential

Project description:The genetic programs that maintain leukemia stem cell (LSC) self-renewal and oncogenic potential have been well defined, however the epigenetic landscape that determines their cellular identity and functionality has not been established. We report that LSCs in MLL-associated leukemia are maintained in an epigenetic state defined by relative genome-wide high-level H3K4me3 methylation and low level H3K79me2. LSC differentiation is associated with dynamic reversal of these broad epigenetic profiles and concomitant down-regulation of the LSC maintenance transcriptional program. LSCs also share with embryonic stem cells a large subset of genes with bivalent histone marks related to embryonic development. The histone demethylase KDM5B negatively regulates MLL-induced leukemogenesis demonstrating the crucial role of the H3K4 global methylome for determining leukemia stem cell fate. Investigation of multiple histone modification marks and RNA Pol II in ckit+ and ckit- cells isolated and fractionated from MLL leukemia mice.

2015-06-26 | E-GEOD-60193 | 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