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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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ShRNA Screening Identifies JMJD1C as being required for Leukemia Maintenance (Agilent)

ABSTRACT: We used a mouse model of human AML induced by the MLL-AF9 fusion oncogene, and an epigenetic shRNA library to screen for novel potential drug targets. One of the best candidate drug targets identified in these screens was Jmjd1c. Depletion of Jmjd1c impairs growth and colony formation of mouse MLL-AF9 cells in vitro, as well as establishment of leukemia after transplantation. Depletion of JMJD1C impairs expansion and colony formation of human leukemic cell lines, with the strongest effect observed in the MLL-rearranged ALL cell line, SEM. In both mouse and human leukemic cells, the growth defect upon JMJD1C depletion appears to be primarily due to increased apoptosis, which implicates JMJD1C as a potential therapeutic target in leukemia. To assess the effect of JMJD1C depletion on transcription, we compared the transcriptome of shJMJD1C- and shScr-transduced mouse MLL-AF9 transformed cells 48h after infection. A total of 451 transcripts were detected as changing between the two conditions (FDR<0.25)

ORGANISM(S): Mus musculus

SUBMITTER: Kristian Helin

PROVIDER: E-GEOD-54311 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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shRNA Screening Identifies JMJD1C as being required for Leukemia Maintenance

Project description:We used a mouse model of human AML induced by the MLL-AF9 fusion oncogene, and an epigenetic shRNA library to screen for novel potential drug targets. One of the best candidate drug targets identified in these screens was Jmjd1c. Depletion of Jmjd1c impairs growth and colony formation of mouse MLL-AF9 cells in vitro, as well as establishment of leukemia after transplantation. Depletion of JMJD1C impairs expansion and colony formation of human leukemic cell lines, with the strongest effect observed in the MLL-rearranged ALL cell line, SEM. In both mouse and human leukemic cells, the growth defect upon JMJD1C depletion appears to be primarily due to increased apoptosis, which implicates JMJD1C as a potential therapeutic target in leukemia. To assess the effect of JMJD1C depletion on transcription, we compared the transcriptome of shJMJD1C- and shScr-transduced SEM cells soon after induction of shRNA expression by addition of IPTG to the growth medium. To ensure detecting early changes, 48h was selected as the earliest timepoint displaying JMJD1C depletion and detectable phenotype as monitored by PARP and Caspase 3 cleavage. These observations were consistent across triplicate samples. A total of 138 transcripts were detected as changing between the two conditions (FDR<0.05)

2013-08-22 | E-GEOD-50048 | biostudies-arrayexpress

shRNA Screening Identifies JMJD1C as being required for Leukemia Maintenance

2013-08-22 | GSE50048 | GEO

shRNA Screening Identifies JMJD1C as being required for Leukemia Maintenance (Agilent)

2014-01-23 | GSE54311 | GEO

Effect of loss of Jmjd1c on MLL-AF9 leukemia

Project description:Analysis of gene expression profile of MLL-AF9 leukemia cells 6 days after loss of Jmjd1c. Loss of Jmjd1c induces differentiation and apoptosis in MLL-AF9 leukemia cells. These results provide insight into the role of Jmjd1c in MLL leukemia.

2016-06-09 | GSE75576 | GEO

ChIP-seq of histone marks H3K36, H3K27, and H3K9 in JMJD1C knockout or mutated MLL-AF9 leukemia cells

Project description:We performed genome-wide profiling of H3K9me3, H3K9me1, H3K27me3, and H3K36me3 by ChIP-seq in JMJD1C knockout or mutated MLL-AF9 leukemia cells. For ChIP-seq in JMJD1C mutated cells, we transduced sgRNA targeting the zinc finger, jumonji domain of JMJD1C or Renilla control and sorted on day 6 for GFP (MLL-AF9) Tdtomato (sgRNA) double positive cells. For ChIP-seq in JMJD1C knockout cells, we transduced Jmjd1c flox/flox MLL-AF9 leukemia cells with CRE TdTomato and sorted on day 6 for GFP (MLL-AF9) Tdtomato (CRE) double positive cells. These cells were subjected to ChIP-seq analysis with either H3K27me3, H3K9me3, H3K9me1 (JMJD1C knockout cells) or H3K36me3 (both knockout and mutated cells) antibody. We found increased H3K36me3 level at promoters of differentially expressed genes between control and JMJD1C loss or mutated leukemia cells.

2019-04-12 | GSE129661 | GEO

Effect of loss of Jmjd1c on H3K9me2 level across the genome

Project description:Analysis of H3K9me2 level in MLL-AF9 leukemia cells upon deletion of Jmjd1c. Jmjd1c has been shown to be a H3K9me1/2 demethylase and these results provide insight into its role in MLL-Af9 leukemia

2016-06-09 | GSE75577 | GEO

Single-cell sequencing of JMJD1C Jumonji domain mutated MLL-AF9 Leukemia cells

Project description:We performed single-cell sequencing on mouse MLL-AF9-cas9 leukemia cells 7 days after transduction with sgRNA against Renilla or JMJD1C JmjC domain. We revealed heterogeneity within each population.

2019-04-12 | GSE129662 | GEO

Affymetrix gene arrays of leukemic BM samples from 24 mice including 9 primary

Project description:To identify such targets of leukemia-related miRNAs such as miR-196b, we conducted Affymetrix gene arrays of leukemic BM samples from 24 mice including 9 primary (including 3 each of negative control, MLL-AF9, and miR-196b+MLL-AF9) and 15 secondary (including 3 negative control, 6 MLL-AF9, and 6 miR-196b+MLL-AF9) recipient mice A total of 24 mouse bone marrow samples including 9 primary (including 3 each of negative control, MLL-AF9, and miR-196b+MLL-AF9) and 15 secondary (including 3 negative control, 6 MLL-AF9, and 6 miR-196b+MLL-AF9) obtained from the in vivo mouse bone marrow reconstitution assays were analyzed by use of Affymetrix GeneChip Mouse Gene 1.0 ST Array (Affymetirx, Santa Clara, CA)

2012-08-09 | E-GEOD-34185 | biostudies-arrayexpress

RNA-seq study on MLL-AF9 leukemia cells harboring JMJD1C sgRNAs targeting jumonji and zinc finger domains.

Project description:We transduced clonally MLL-AF9 leukemia cells expressing cas9 with sgRNA targeting the jumonji and zinc finger domains of JMJD1C. GFP (MLL-AF9) and TdTomato (sgRNA) double positive cells were sorted on Day 6 after transduction. Total RNA was isolated followed by mRNA selection. cDNA libraries were generated and NextGen Sequencing was performed.

2019-04-12 | GSE129660 | GEO

RNA-seq profiling of murine Tet-off MLL-AF9; NRAS acute myeloid leukemia at different timepoints upon doxycycline-induced MLL-AF9 down-regulation.

Project description:Using an acute myeloid leukemia (AML) mouse model driven by tet-regulated MLL-AF9 (fusion between the gene MLL1 (KMT2A/MLL) and MLLT3 (AF9)) co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we investigated the effect of modulating the expression of the MLL-AF9 fusion oncogene on the transcriptome and proteome of established murine AML. Treatment in vitro or in vivo of these Tet-off MLL-AF9 AMLs with doxycycline (DOX) results in the efficient down-regulation of the expression of the driver oncogene MLL-AF9. RNA sequencing analysis was performed on primary Tet-Off MLL-AF9 AML cells obtained from the spleen of leukemic animals and cultured in vitro for either 2 or 4 days in the presence of doxycycline (1μg/ml) (DOX= down-regulation of MLL-AF9) or left untreated (UT).

2021-12-31 | GSE108326 | GEO

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