Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microarray data from L-GMPs and GMPs

ABSTRACT: A leukemia cell fraction highly enriched for LSCs was generated in a mouse model of AML induced by co-expression of MLL target genes Hoxa9 and Meis1. Limit dilution transplantation analyses performed on various prospectively isolated leukemia cell subpopulations revealed that cells capable of transplanting AML to syngeneic recipient mice (the operational definition of LSCs) were highly enriched in the leukemia cell fraction displaying an immunophenotype (Lin- Sca1- c-kit+ CD16/32+ CD34+) comparable to normal GMPs, referred to as L-GMPs. For the purpose of identifying genes that are differentially expressed in LSCs, microarray expression profiling was performed on L-GMPs (from leukemic mice) and GMPs (from normal mouse BM) purified by flow cytometry.

ORGANISM(S): Mus musculus

PROVIDER: GSE64773 | GEO | 2015/10/02

SECONDARY ACCESSION(S): PRJNA271850

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Acute Myeloid Leukemia iPSCs reveal a role for RUNX1 in the maintenance of human Leukemia Stem Cells

Project description:Leukemia stem cells (LSCs) in acute myeloid leukemia (AML) are believed to possess distinct biological properties than the bulk AML cells, but their rarity and the unavailability of universal immunophenotypic markers for their prospective isolation hampers their study. We report that hematopoietic cells from genetically clonal AML patient-derived induced pluripotent stem cells (iPSCs) contain two morphologically and immunophenotypically distinct subpopulations: a cell fraction with a hematopoietic stem cell (HSC) immunophenotype exhibiting adherent growth which we termed induced leukemai stem cells (iLSCs) and a non-adherent fraction of more differentiated cells, which we termed induced blasts (iBlasts). Through fate-tracking experiments, xenotransplantation and single cell transcriptomics, we show that iLSCs cells reside on the apex of a phenotypic and functional hierarchy and fulfill the hallmark features of leukemia stem cells. Through integrative genomics studies of their transcriptome and chromatin landscape, we derive an LSC 16-gene set that predicts patient survival and identify RUNX1 as a new dependency of AML LSCs.

2020-02-13 | GSE124992 | GEO

Effect of Dot1l deletion on LSKs and GMPs

Project description:We wanted to investigate the effects of Dot1l deletion on gene expression in LSKs and GMPs of C57/BL6 mice Aberrant Hox gene activation is a recurrent feature in several different types of human leukemia, including leukemias with rearrangements of the mixed lineage leukemia (MLL) gene. In this study, we demonstrate that Hox gene expression is controlled by higher degree H3K79 methylation in acute myeloid leukemia (AML). We show that the deposition of progressive H3K79 methylation states at the genomic loci of critical Hox genes is dependent on the interaction of the H3K79 methyltransferase Dot1l with Af10, a protein that is found in the Dot1l complex isolated from diverse cell types. Furthermore, abrogation of the Dot1l-Af10 interaction reverses aberrant epigenetic profiles found in the leukemia epigenome and impairs the transforming ability of mechanistically distinct AML oncogenes. Lineage negative Sca-1 positive Kit positive (LSK) cells and granulocyte macrophage progenitors (GMPs) were sorted from Dot1 wt/wt x Mx-Cre mice or Dot1l fl/fl x Mx-Cre mice were injected with PIPC. PIPC injection induced biallelic deletion of the Dot1l allele in the Dot1l fl/fl mice but not the Dot1l wt/wt mice. The Dot1l wt/wt LSKs and GMPs were compared to the Dot1l -/- counterparts by RNA extraction and Microarrays.

2014-09-08 | E-GEOD-54498 | biostudies-arrayexpress

Microarray data of human MLLr AML cells with or without CD93 expression

Project description:Leukemia stem cells (LSCs) share several crucial properties with hematopoietic stem cells (HSCs) including self-renewal, cell cycle quiescence, and expression of a CD34+CD38- immunophenotype, which complicates efforts to eradicate AML by therapeutically targeting LSCs without adversely affecting HSCs. Here we report that CD93, a C-type lectin transmembrane receptor, is preferentially expressed on the cell surface of LSCs compared with HSCs in the genetic subtype of AML with genomic rearrangements of the MLL gene. LSCs that selectively express CD93 are actively cycling, and highly enriched for xeno-engraftment potential, yet comprise a minor component of an otherwise quiescent CD34+CD38- compartment of human AML. Notably, CD93 is required for LSC function in MLL leukemogenesis, and is not simply a passive surface marker co-expressed on LSCs. Thus, CD93 selectively marks and essentially maintains LSCs, and identifies them as predominantly cycling, non-quiescent leukemia-initiating cells in MLL-rearranged AML.

2015-10-02 | GSE64776 | GEO

Expression data from bone marrow derived granulocyte monocyte precursors (GMPs) from wt -, Gfi1 knock-out -, human-Gfi1-SNP36N knock in and human wt-Gfi1 knock in mice

Project description:The incidence of cancer is not only influenced by exposure to environmental factors such as toxic substances and chemotherapy, but is also a result of individual predispositions. Single Nucleotide Polymorphisms (SNPs) represent one such individual predisposition to cancer1. Gfi136N is a SNP in the coding region of the gene “Growth factor independence 1 (Gfi1)” predisposing to development of Acute myeloid leukemia (AML). However, the mechanisms how this polymorphism is associated with AML are unknown. Here we present a mouse model in which the presence of Gfi136N leads to altered epigenetic modifications in the myeloid progenitor fraction “Granulocytic Monocytic Progenitor (GMP)” and demonstrates how this might predispose to AML. Presence of Gfi136N leads to a different epigenetic programming of the GMPs resulting in higher levels of the leukemogenic transcription factor Hoxa9. To our knowledge, this is the first mouse model of a SNP leading to epigenetic changes. Thus, SNPs not only result in an altered structure or expression level of certain proteins but here we show that SNPs might also lead to different cancer related epigenetic modifications. We used microarrays to detail the changes in the program of gene expression of GMPs induced by the knock in of human Gfi1 variants in the mouse Gfi1 locus Bone marrow derived granulocyte monocyte precursors (GMPs) from wt.-,Gfi1 knock-out.-, human Gfi1-knock in and human Gfi1-SNP36N knock in mice were collected by fluorescence activated cell sorting (FACS) for total RNA extraction and gene expression analysis on affymetrix mouse Gene 1.0 ST arrays. We aimed to identify differentially regulated target genes of the human Gfi1-SNP36N variant in a mouse model system which mit contribute to the development of acute myeloid leukemia (AML).

2012-11-22 | E-GEOD-25551 | biostudies-arrayexpress

Effect of Dot1l deletion on LSKs and GMPs

2014-09-08 | GSE54498 | GEO

The Quantitative Analysis of Transcriptomes Derived From Ezh2- or Ezh1/2-Deleted Leukemia Stem Cells of Murine Acute Myloid Leukemia

Project description:We report dual genetic delstion of Ezh1/2 in murine AML model induced cell cyle progression of quiescent LSCs and cell differentiation of LSCs. To investigate the underlying mechanism by which Ezh1/2 regulate quiescent LSCs and maintein the stemness of LSCs, we performed RNA sequencing of L-GMPs derived from Ezh2- and Ezh1/2-deleted AML mice.

2017-03-11 | GSE96061 | GEO

Dormant leukemia stem cells reinforced by chemotherapy drive early treatment failure in acute myeloid leukemia patients [scRNA_PT]

Project description:Acute myeloid leukemia is characterized by a minor fraction of primitive leukemia stem cells (LSCs) that sustain disease propagation and may be at the origin of late relapse. Yet, LSC contribution to early therapy resistance and AML regeneration remains controversial. We prospectively identified LSCs in NPM1-mutated AML patients and xenografts by means of a microRNA-126 reporter and single cell RNA sequencing, precisely discriminating LSCs from regenerating hematopoiesis, and assessed their longitudinal response to chemotherapy. We here show that chemotherapy resulted in distinct outcomes within AML subpopulations: while the bulk leukemia proliferated and differentiated with expression of oxidative-phosphorylation signatures, persisting miR-126high LSCs enforced protective stemness and dormancy features, along with a generalized inflammatory and senescence-associated response. miR-126high LSCs were enriched at diagnosis in patients with chemotherapy-refractory AML. We derived a novel miR-126high LSC transcriptional signature, which robustly stratified patients for overall survival in large AML cohorts, shining the spotlight on LSCs as determinants of early therapy resistance.

2023-02-06 | GSE185991 | GEO

Dormant leukemia stem cells reinforced by chemotherapy drive early treatment failure in acute myeloid leukemia patients [scRNA_PDX]

2023-02-06 | GSE185834 | GEO

Dormant leukemia stem cells reinforced by chemotherapy drive early treatment failure in acute myeloid leukemia patients [bulkRNA]

2023-02-06 | GSE185824 | GEO

Distinct leukemogenic mechanism of acute promyelocytic leukemia based on genomic structure of PML-RARα fusion gene

Project description:Leukemic stem cells (LSCs) of acute myeloid leukemia (AML) are enriched in CD34+CD38- fraction, and self-renewing LSCs hierarchically organize and maintain the AML populations. In acute promyelocytic leukemia (APL), which is driven by PML-RARα fusion genes, the presence of LSCs has long been unidentified, due to the difficulty of efficient reconstitution of human APL in the immunodeficient mice. Here, we show that LSCs of short type isoform APL, subtype of APL defined by different breakpoint of PML gene, concentrate in CD34+CD38- fraction and express T cell immunoglobulin mucin-3 (TIM-3) as in other non-APL AML. Short type APL cells exhibited distinct gene expression signatures including LSCs-related genes from other types of APL. Moreover, CD34+CD38-TIM-3+ short type APL cells efficiently reconstituted huma APL in xenograft models with high penetration, whereas CD34- more differentiated APL cells did not. Furthermore, CD34+CD38-TIM-3+ short type APL cells also reconstituted leukemia in the serial transplantation. Thus, short type APL is showing hierarchically organized by self-renewing APL-LSCs same as in other types of AML. The identification of LSCs in a subset of APL and establishment of efficient patient derived xenograft model would contribute to further understanding of APL leukemogenesis and devising individual treatment for eradication of APL LSCs.

2022-07-05 | GSE207432 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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