Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA396027 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We FACS purified L-GMP cells (GFP+ tdTom+ c-Kit+ Sca-1+ CD16/32+ CD34+) from mice transplanted with post-transformed Scr or miR-99 KD MLL-AF9 bone marrow and performed RNA-sequencing, demonstrating miR-99 KD results in induction differentiation and enrichment for a normal GMP gene expression signature
2017-07-27 | GSE101957 | GEO
Project description:We FACS-purified GFP+ LSK cells from mice transplanted with stably engrafted miR-99 KD and Scr HSCs and performed RNA-sequencing, demonstrating miR-99 KD results in significant depletion of hematopoietic stem cell gene expression signature and induces a differentiated progenitor gene expression signature.
2017-07-27 | GSE101903 | GEO
Project description:Leukemia initiating cells (LICs) of acute myeloid leukemia (AML) may arise from self-renewing hematopoietic stem cells (HSCs) and from committed progenitors. However, it remains unclear how leukemia-associated oncogenes instruct LIC formation from cells of different origins and if differentiation along the normal hematopoietic hierarchy is involved. Here, using murine models with the driver mutations MLL-AF9 or MOZ-TIF2, we found that regardless of the transformed cell types, myelomonocytic differentiation to the granulocyte macrophage progenitor (GMP) stage is critical for LIC generation. Blocking myeloid differentiation through disrupting the lineage-restricted transcription factor C/EBPa eliminates GMPs, blocks normal granulopoiesis, and prevents AML development. In contrast, restoring myeloid differentiation through inflammatory cytokines “rescues” AML transformation. Our findings identify myeloid differentiation as a critical step in LIC formation and AML development, thus guiding new therapeutic approaches. Primary KSL, CMP, and GMP cells from wildtype controls and C/Ebpa knockouts were used for RNA extraction and hybridization on Affymetrix microarrays. We also compared the microarray samples of leukemic granulocyte macrophage progenitor compartments (L-GMPs) from MLL-AF9 transformed control or cytokine rescued C/EBPa KO leukemic mouse bone marrow and their secondary recipients with those non-Leukemia KSLs and CMPs from MLL-AF9 transduecd KO recipients with no leukemia development.
2015-08-04 | E-GEOD-71687 | biostudies-arrayexpress
Project description:Leukemia initiating cells (LICs) of acute myeloid leukemia (AML) may arise from self-renewing hematopoietic stem cells (HSCs) and from committed progenitors. However, it remains unclear how leukemia-associated oncogenes instruct LIC formation from cells of different origins and if differentiation along the normal hematopoietic hierarchy is involved. Here, using murine models with the driver mutations MLL-AF9 or MOZ-TIF2, we found that regardless of the transformed cell types, myelomonocytic differentiation to the granulocyte macrophage progenitor (GMP) stage is critical for LIC generation. Blocking myeloid differentiation through disrupting the lineage-restricted transcription factor C/EBPa eliminates GMPs, blocks normal granulopoiesis, and prevents AML development. In contrast, restoring myeloid differentiation through inflammatory cytokines “rescues” AML transformation. Our findings identify myeloid differentiation as a critical step in LIC formation and AML development, thus guiding new therapeutic approaches. Primary KSL, CMP, and GMP cells from wildtype controls and C/Ebpa knockouts were used for RNA extraction and hybridization on Affymetrix microarrays. We also compared the microarray samples of leukemic granulocyte macrophage progenitor compartments (L-GMPs) from MLL-AF9 transformed control or cytokine rescued C/EBPa KO leukemic mouse bone marrow and their secondary recipients with those non-Leukemia KSLs and CMPs from MLL-AF9 transduecd KO recipients with no leukemia development.
2014-09-17 | E-GEOD-61468 | biostudies-arrayexpress
Project description:We FACS purified GFP+ cells 2 days post-transduction of LSK (Lin-Negative c-Kit+ Sca1+) cells with miR-99 KD and Scr lentiviral vectors and performed RNA-sequencing; this allowed us to identify potential miR-99 target genes for inclusion in the shRNA library
2017-07-27 | GSE101902 | GEO
Project description: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.
2015-10-02 | GSE64773 | GEO
Project description:Chromatin immunoprecipitation (ChIP) for H3K27me3 followed by Solexa sequencing in WT and Ezh2-null leukemic cells from primary and secondary recipients. Leukemic cells from primary and secondary recipients of MLL-AF9-transduced WT and Ezh2-null cells were sorted for GFP and YFP expression and analyzed by Chip-Seq.
2012-02-22 | E-GEOD-34962 | biostudies-arrayexpress
Project description:Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect. To investigate the genetic program regulated by KDM1A in murine MLL-AF9 AML cells enriched for LSCs, we compared the transcriptome of KIT+Gr1+ control and Kdm1a KD cells using exon arrays soon after initiation of KD. At this time, there was no immunophenotypic evidence of differentiation in Kdm1a KD cells. Exonic expression values were condensed into gene-level expression summaries, which represent the mean expression value of the probe sets targeting the length of a given protein coding gene. Three separate samples from two different animals were used. Kdm1a KD samples were compared with control samples. Total six arrays.
2012-03-28 | E-GEOD-36347 | biostudies-arrayexpress
Project description:Despite significant efforts to improve therapies for acute myeloid leukemia (AML), clinical outcomes remain poor. Understanding the mechanisms that regulate the development and maintenance of leukemic stem cells (LSC) is important to reveal new therapeutic opportunities. We have identified CD97, a member of the adhesion class of G-protein coupled receptors (GPCRs), as a frequently upregulated antigen of AML blasts that is a critical regulator of blast function. High levels of CD97 correlate with poor prognosis, and silencing of CD97 reduces disease aggressiveness in vivo. In order to analyze the functional pathways associated with CD97 expression, we generated RNA-sequence data from scrambled shRNA transfected (s-shRNA) and CD97 KD human AML cell line HL60, as well as from MLL-AF9 (MA9) transduced GMPs isolated from CD97-/- and WT mice. These phenotypes are due to CD97’s function to promote proliferation, survival, and the maintenance of the undifferentiated state in leukemic blasts. Collectively, our data credential CD97 as a promising therapeutic target on LSCs in AML.
2019-07-30 | GSE135028 | GEO
Project description:miR-101 has been reported as a tumor suppressor in several types of cancer. However, its role in AML is still unknown. In this study, we restored the expression of miR-101 in MLL-AF9 transduced LSK cells by introducing a retroviral miR-101 expression vector. To identify miR-101-regulated gene expression, we performed genome-wide gene expression analysis on GFP+ MLL-AF9-transduced LSK cells overexpressing miR-101 versus control vector. Our gene expression analysis and subsequent functional studies demonstrate that enforced expression of miR-101 has antitumor effects on the development of MLL-rearranged AML. Each group has 3 samples.
2019-07-03 | E-MTAB-7344 | biostudies-arrayexpress