We found that the non-essential amino acid L-Proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells (ESCs) into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic stem cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the transcriptome
L-Proline induces a mesenchymal-like invasive program in embryonic stem cells by remodeling H3K9 and H3K36 methylation.
Cell line
View SamplesTo examine Ikaros tumor suppressor mechanisms, we have utilized inducible RNAi to dynamically restore endogenous Ikaros expression in T-ALL driven by its knockdown. This causes rapid transcriptional repression of Notch1 and associated targets including Myc, even in leukemias harboring spontaneous activating Notch1 mutations (producing aberrant ICN1) similar to those found in 60% of human T-ALL. Ikaros restoration results in sustained regression of Notch1-wild type leukemias while endogenous or engineered ICN1 expression promotes rapid disease relapse, indicating that ICN1 functionally antagonizes Ikaros in T-ALL. Overall design: RNA-seq was performed on T-ALL (Vav-tTA;TRE-GFP-shIkaros primary leukemia ALL211) cells isolated from two untreated and two 3-day Dox-treated mice.
Activated Notch counteracts Ikaros tumor suppression in mouse and human T-cell acute lymphoblastic leukemia.
No sample metadata fields
View SamplesTo examine Ikaros tumor suppressor mechanisms, we have utilized inducible RNAi to dynamically restore endogenous Ikaros expression in T-ALL driven by its knockdown. This causes rapid transcriptional repression of Notch1 and associated targets including Myc, even in leukemias harboring spontaneous activating Notch1 mutations (producing aberrant ICN1) similar to those found in 60% of human T-ALL. Ikaros restoration results in sustained regression of Notch1-wild type leukemias while endogenous or engineered ICN1 expression promotes rapid disease relapse, indicating that ICN1 functionally antagonizes Ikaros in T-ALL. Overall design: RNA-seq was performed on T-ALL (Vav-tTA;TRE-GFP-shIkaros primary leukemia ALL65) cells isolated from three untreated and three 3-day Dox-treated mice. There were two sequencing runs of each RNA sample.
Activated Notch counteracts Ikaros tumor suppression in mouse and human T-cell acute lymphoblastic leukemia.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Notch pathway activation targets AML-initiating cell homeostasis and differentiation.
Sex, Specimen part, Cell line, Treatment
View SamplesExpression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation.
Notch pathway activation targets AML-initiating cell homeostasis and differentiation.
Specimen part, Cell line, Treatment
View SamplesTo determine role of Notch signaling in AML leukemia initiating cells we used a conditional mouse knock-in model of Notch1-IC to induce Notch1-IC expression in MLL-AF9 transformed LGMP. WT and Notch1-IC+ LGMP were analyzed to determined genes controlled by Notch signaling.
Notch pathway activation targets AML-initiating cell homeostasis and differentiation.
Sex, Specimen part
View SamplesTriplicate RNA-seq expression analysis of bone marrow pre-B cells isolated from mice, to demonstrate repertoire at the IgH locus Overall design: Triplicate RNA-seq expression analysis of bone marrow pre-B cells
Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia.
No sample metadata fields
View SamplesHypomorphic mutations of the transcription factor PAX5 occur in one third of B-progenitor acute lymphoblastic leukemias (B-ALLs). To identify PAX5-regulated genes in B-ALL, here we employ inducible expression of PAX5 in a human B-ALL cell line (REH) that harbors a loss-of-function mutation in PAX5. In this model, inducing PAX5 expression is associated with competitive disadvantage. Overall design: Comparison of REH cell lines with Dox-inducible expression of PAX5-IRES-GFP, or control GFP alone. GFP positive cells were isolated by FACS.
Pax5 loss imposes a reversible differentiation block in B-progenitor acute lymphoblastic leukemia.
No sample metadata fields
View SamplesWe performed RNA-sequencing in c-Kit+ cells that were infected with retroviruses expressing shRNAs for Renilla, Rad21, Smc1a, Smc3 or Stag2. These cells were grown in methylcellulose (M3434) for either one passage (P1) or replated for five passages (P5). Overall design: RNA-sequencing control (Ren) and cohesin (Rad21, Smc1a, Smc3 and Stag2) knockdown cells.
Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms.
Specimen part, Subject
View SamplesWe performed RNA-sequencing in LSK cells (Lin(neg)/c-Kit(+)/Sca-1(+)) from shRNA mice carrying an shRNA for Renilla, Smc1a or Stag2. Overall design: RNA-sequencing control (Renilla) and cohesin (Smc1a and Stag2) knockdown cells.
Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms.
Specimen part, Subject
View Samples