Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA302785 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptional profiling of murine bone marrow c-kit+, Sca-1+ lineage neative (KSL) cells from p21CDKN1a-/- and p21+/+ overexpressing Flt3/ITD. The goal was to determine the effect on global gene expression by loss of p21 in Flt3/ITD transformed KSL cells Internal tandem duplication (ITD) mutations in the Flt3 gene (Flt3-ITD) are associated with poor prognosis in patients with acute myeloid leukemia (AML). Few inhibitors of Flt3-ITD are effective against Flt3-ITD+ AML due to the development of drug-resistance. In this study, we demonstrate that Flt3-ITD activates a novel pathway involving p21Cdkn1a (p21) and pre-B cell leukemia transcription factor 1 (Pbx1) that attenuates Flt3-ITD cell proliferation and is involved in the development drug resistance. Flt3-ITD up-regulated p21 expression in mouse bone marrow c-kit+-Sca-1+-Lin- (KSL) cells and in Ba/F3 cells. Loss of p21 expression enhanced growth factor-independent proliferation and sensitivity to cytarabine as a consequence of enriching the S+G2/M phase population concomitant with a significant increase in the expression of Pbx1, but not Evi-1, in Flt3-ITD+ cells. This enhancement of cell proliferation by loss of p21 was partially abrogated when Pbx1 expression was silenced in Flt3-ITD+ primary bone marrow colony-forming cells (CFCs) and Ba/F3 cells. Antagonizing Flt3-ITD using AC220, a selective inhibitor of Flt3-ITD, decreased the expression of p21, coincident with the up-regulation of Pbx1 mRNA and a rapid decline in the number of viable Flt3-ITD+ Ba/F3 cells, however the cells eventually became refractory to AC220. Overexpressing p21 in Flt3-ITD+ Ba/F3 cells delayed the emergence of cells refractory to AC220, whereas silencing p21 accelerated their development. These data demonstrate that Flt3-ITD is capable of inhibiting the proliferation of Flt3-ITD+ cells through the p21/Pbx1 axis and that antagonizing Flt3-ITD contributes to the subsequent development of cells refractory to Flt3-ITD inhibitor by disrupting p21 expression. biological replicates: 3 KSL cell replicates overexpressing ITD-Flt3 from p21+/+ and p21-/- cells, 1 KSL cell replicate from p21+/+ and p21-/- cells
2015-11-20 | E-GEOD-75200 | biostudies-arrayexpress
Project description:Transcriptional profiling of murine bone marrow c-kit+, Sca-1+ lineage neative (KSL) cells from p21CDKN1a-/- and p21+/+ overexpressing Flt3/ITD. The goal was to determine the effect on global gene expression by loss of p21 in Flt3/ITD transformed KSL cells Internal tandem duplication (ITD) mutations in the Flt3 gene (Flt3-ITD) are associated with poor prognosis in patients with acute myeloid leukemia (AML). Few inhibitors of Flt3-ITD are effective against Flt3-ITD+ AML due to the development of drug-resistance. In this study, we demonstrate that Flt3-ITD activates a novel pathway involving p21Cdkn1a (p21) and pre-B cell leukemia transcription factor 1 (Pbx1) that attenuates Flt3-ITD cell proliferation and is involved in the development drug resistance. Flt3-ITD up-regulated p21 expression in mouse bone marrow c-kit+-Sca-1+-Lin- (KSL) cells and in Ba/F3 cells. Loss of p21 expression enhanced growth factor-independent proliferation and sensitivity to cytarabine as a consequence of enriching the S+G2/M phase population concomitant with a significant increase in the expression of Pbx1, but not Evi-1, in Flt3-ITD+ cells. This enhancement of cell proliferation by loss of p21 was partially abrogated when Pbx1 expression was silenced in Flt3-ITD+ primary bone marrow colony-forming cells (CFCs) and Ba/F3 cells. Antagonizing Flt3-ITD using AC220, a selective inhibitor of Flt3-ITD, decreased the expression of p21, coincident with the up-regulation of Pbx1 mRNA and a rapid decline in the number of viable Flt3-ITD+ Ba/F3 cells, however the cells eventually became refractory to AC220. Overexpressing p21 in Flt3-ITD+ Ba/F3 cells delayed the emergence of cells refractory to AC220, whereas silencing p21 accelerated their development. These data demonstrate that Flt3-ITD is capable of inhibiting the proliferation of Flt3-ITD+ cells through the p21/Pbx1 axis and that antagonizing Flt3-ITD contributes to the subsequent development of cells refractory to Flt3-ITD inhibitor by disrupting p21 expression.
2015-11-20 | GSE75200 | GEO
Project description:The study was a comparison of gene expression using RNA-seq. We analyzed the stem and progenitor cells from WT and Vav-cre+ Tet2fl/fl Flt3-ITD (T2F3) mice. We isolated stem cells LSK (lin- sca+ kit+) and granulocyte-macrophage progenitors GMP (lin- sca- kit+ fcgr+ cd34+) cells from bone marrow. Comparisons were made across genotypes WT vs. T2F3 and cell types LSK vs. GMP.
2015-05-01 | GSE57244 | GEO
Project description:The study was a comparison of gene expression using RNA-seq. We analyzed the stem and progenitor cells from WT and Vav-cre+ Tet2fl/fl Flt3-ITD (T2F3) mice. We isolated stem cells LSK (lin- sca+ kit+) and granulocyte-macrophage progenitors GMP (lin- sca- kit+ fcgr+ cd34+) cells from bone marrow. Comparisons were made across genotypes WT vs. T2F3 and cell types LSK vs. GMP. Comparison of WT and Tet2-/-Flt3ITD bone marrow stem and progenitor cells.
2015-05-01 | E-GEOD-57244 | biostudies-arrayexpress
Project description:Transcriptomes of 1141 single cells isolated from bone marrow of induced R26rtTA/rtTA/Col1A1H2B-GFP/H2B-GFP mice; the following cell types were sorted: Megakaryocyte Progenitor (MkP): lineage- Sca-1- c-kit+ CD41+ CD150+; Multipotent Progenitor (MPP): lineage- Sca-1+ c-kit+ CD48- CD150- ; Hematopoietic Stem Cell (HSC):lineage- Sca-1+ c-kit+ CD48- CD150+; E34 HSC: lineage- Sca-1+ c-kit+ CD48- CD150+ CD201hi CD34-/lo; Restricted hematopoietic progenitor 1 (HPC-1): lineage- Sca-1+ c-kit+ CD48+ CD150-; lineage- kit+ CD41- CD150- cells; lineage- kit+ CD150+ cells.
2022-04-28 | GSE159390 | GEO
Project description:Analysis of MHCII-high (MHCII-hi) and MHCII-low (MHCII-lo) hematopoietic stem cells (Lineage-Sca-1+c-Kit+CD150+Flt3-CD48-). The two population of hematopoietic stem cell (HSC) were purified from the bone marrow of 12 months old (12 mo) mice. Results provide insight into the role of MHCII in HSC.
2023-08-08 | GSE211206 | GEO
Project description:Analysis of MHCII-high (MHCII-hi) and MHCII-low (MHCII-lo) hematopoietic stem cells (Lineage-Sca-1+c-Kit+CD150+Flt3-CD48-). The two population of hematopoietic stem cell (HSC) were purified from the bone marrow of 5 months old WT mice (Ctrl). Results provide insight into the role of MHCII in HSC.
2023-08-08 | GSE211203 | GEO
Project description:Analysis of MHCII-high (MHCII-hi) and MHCII-low (MHCII-lo) hematopoietic stem cells (Lineage-Sca-1+c-Kit+CD150+Flt3-CD48-). The two population of hematopoietic stem cell (HSC) were purified from the bone marrow of mice at 3 months post 5 Gy total body irradiation (IR). Results provide insight into the role of MHCII in HSC.
2023-08-08 | GSE211205 | GEO
Project description:Examination of gene expression patterns in lineage negative FLT3-ITDâ and pMIG-transduced BM cells via microarray study. We performed a global mRNA profiling analysis of murine Linâ FLT3-ITD+ cells compared to empty-vector controls, purified 48h after transduction. We examined association patterns of FLT3-ITD and pMIG cells and identified a specific gene expression signature associated with FLT3-ITD signalling. Total RNA obtained from isolated lineage negative BM cells subjected to 48h of FLT3-ITD signalling compared to empty vector control.
2016-08-22 | E-GEOD-79040 | biostudies-arrayexpress
Project description:Cytokines control the biology of hematopoietic stem and progenitor cells in part through the transcription factors STAT5a/b. CCN3/NOV has been reported as a positive regulator of hematopoietic stem and progenitor cells. We report microarray analyses of Lineage- Sca-1+ c-Kit+ (KSL) cells in the presence and absence of STAT5a/b. Expression of the ccn3 gene was induced over 100-fold in control, but not STAT5a/b-null cells, upon stimulation with a cocktail containing IL-3, IL-6, SCF, TPO and Flt3 ligand. Among the cytokines, IL-3 elevated ccn3 mRNA level in Lineage- c-Kit+ (KL) cells and 32D cells. ChIP assays using 32D cells revealed IL-3-induced binding of STAT5a/b to a GAS site in the ccn3 gene promoter. This is the first report to link two molecules with importance in the regulation of HSCs, CCN3 and STAT5a/b. We report that the regulation and expression of the ccn3 gene is directly controlled by IL-3 through the transcription factors STAT5a/b. Six Control and Six Stat5a/b-null KSL cells, including three biological replications, were unstimulated or stimulated with a cocktail containing IL-3, IL-6, SCF, TPO and FL.
2010-08-25 | E-GEOD-20684 | biostudies-arrayexpress