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SRP152817
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy of T cell progenitors that in most patients is associated with activating mutations in the NOTCH1 pathway. Recent reports have indicated a link between Ca2+ homeostasis in the endoplasmic reticulum (ER), the regulation of NOTCH1 signaling and T-ALL. Here we investigated the role of store-operated Ca2+ entry (SOCE) in T-ALL. SOCE is a Ca2+ influx pathway that is mediated by the plasma membrane Ca2+ channel ORAI1 and its activators STIM1 and STIM2. Deletion of STIM1 and STIM2 in leukemic cells abolished SOCE and significantly prolonged the survival of mice in a NOTCH1-driven model of T-ALL. The survival advantage was unrelated to leukemia development and leukemic cell burden, but was associated with the SOCE-dependent ability of malignant T lymphoblasts to cause inflammation in leukemia-infiltrated organs. Mice with wildtype T-ALL showed a severe necroinflammatory response in their bone marrow, which was absent in mice with Stim1/2-/- leukemia. Several signaling pathways previously linked to cancer-induced inflammation were downregulated in Stim1/2-/- leukemic cells, likely accounting for less aggressive leukemia progression and prolonged survival of mice. Our study shows that T-ALL is associated with inflammation of leukemia-infiltrated organs and that SOCE controls the proinflammatory effects of leukemic T lymphoblasts. Overall design: Bone marrow leukemic cell were isolated from WT and Stim1/2-/- leukemic mice, 21 days after leukemia induction and their mRNA profiles were generated by deep sequencing, in triplicate.
Publication Title
STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2).
Publication Title
In vivo mapping of notch pathway activity in normal and stress hematopoiesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy characterized by infiltration of the bone marrow and other sites with transformed T cell progenitors. The role of tissue microenvironments in the pathogenesis of T-ALL or any other type of acute leukemia is little understood. In delineating interactions between T-ALL cells and their environment, we initially found that T-ALL cells express high surface levels of the chemokine receptor CXCR4. Intravital imaging of an intact tibia revealed T-ALL cells in direct contact with bone marrow stromal cells producing the CXCR4 ligand, CXCL12. Genetic targeting of CXCR4 on T-ALL cells resulted in a marked reduction of leukemia burden and prolonged disease remission, and disruption of the CXCL12/CXCR4 axis using small molecule inhibitors prevented T-ALL progression in a primary xenograft model. Finally, we were able to show that CXCR4 inhibition significantly decreased expression of Myc and its target genes. Myc expression is a key regulator of T-ALL leukemia initiating cell (LIC) activity, suggesting that CXCR4 inhibition can suppress LIC activity by silencing the Myc response in T-ALL cells. Our data suggest that targeting of CXCL12/CXCR4 signaling could be a powerful new tool for combating T-ALL, a disease with no current targeted therapies. Overall design: Mouse T-ALL cells were treated ex vivo with Cxcr4 inhibitor AMD3100 or vehicle control. Additionally, mouse T-ALL primary tumors were isolated from control (Cxcr4+/+) or knockout (Cxcr4-/-) animals. Total RNA was extracted from samples using the RNeasy Plus Mini Kit (Qiagen). Samples were then subject to PolyA selection using oligo-dT beads (Life Technologies, Carlsbad, CA) according to the manufacturer''s instructions. The resulting RNA samples were then used as input for library construction using the dUTP method as described by Parkhomchuck et al., 2009. RNA libraries were then sequenced on the Illumina HiSeq 2500 using 50bp single-end reads.
Publication Title
CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
LRAT knockout mice on vitamin A sufficient or deficient diets were compared to age-matched wildtype mice on a vitamin A sufficient diet
Publication Title
Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
LRAT knockout mice on vitamin A sufficient or deficient diets were compared to age and gender matched wildtype mice on a vitamin A sufficient diet
Publication Title
Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Effects of vitamin A deficiency in the postnatal mouse heart: role of hepatic retinoid stores.
Sample Metadata Fields
Sex, Specimen part
View Samples