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Series GSE68462 Query DataSets for GSE68462
Status Public on Jun 29, 2016
Title RNA sequencing expression analysis of murine Tet-off MLL-AF9;NRAS acute myeloid leukemia cells over-expressing Id2 and upon MLL-AF9 withdrawal
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by tet-regulated MLL-AF9 co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in Tet-Off MLL-AF9 AML cells in vitro partially phenocopies MLL-AF9 depletion and results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. To compare gene expression changes associated with enforced Id2 expression and MLL-AF9 withdrawal, RNA sequencing analysis was performed on Tet-off MLL-AF9 cells transduced with an Id2 over-expressing or a control vector, or upon MLL-AF9 dox-inducible knock-down.
Overall design Primary AMLs driven by Tet-off inducible MLL/AF9 expression linked to dsRED reporter, in association with oncogenic NRASG12D (Tet-off MLL-AF9) were generated by reconstituting lethally irradiated congenic mice with foetal liver cells co-transduced with a Tet-Off-MLL-AF9-dRED retroviral vector and a second vector co-expressing NRASG12D together with the Tet-Off responsive transcriptional activator. RNA sequencing analysis sequencing analysis was performed on Tet-Off MLL-AF9/dsRED+ AML cells treated in vitro with doxycycline (DOX) for 4 days to inactivate MLL-AF9 expression or left untreated (UT). For the Id2 over-expression experiment, Tet-Off MLL-AF9/dsRED+ AML cells were transduced in vitro with an Id2-GFP or a control-GFP retroviral vector. Viable GFP-positive cells were FACS-sorted 2 days after transduction and used for RNA sequencing analysis.
Contributor(s) Ghisi M, Masson F, Li J, Kratina T, Vidacs E, Doyle M, Zuber J, Dickins RA, Dawson MA, Corcoran LM, Belz GT, Johnstone RW
Citation(s) 27374225
Submission date May 01, 2015
Last update date May 15, 2019
Contact name Margherita Ghisi
Organization name Peter MacCallum Cancer Centre
Department Research
Lab Gene Regulation
Street address St Andrews Place
City Melbourne
State/province Victoria
ZIP/Postal code 3002
Country Australia
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (14)
GSM1672265 1-1-MA9-CNT
GSM1672266 2-1-MA9-ID2
GSM1672267 3-2-MA9-CNT
This SubSeries is part of SuperSeries:
GSE68463 Id2 and E proteins orchestrate the initiation and maintenance of MLL-rearranged acute myeloid leukemia
SRA SRP057876
BioProject PRJNA282927

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Supplementary file Size Download File type/resource
GSE68462_ID2-CNT_log_dig_matrix.txt.gz 628.7 Kb (ftp)(http) TXT
GSE68462_NormalizedMatrix_TRIMA4dDOX_Paper.txt.gz 846.8 Kb (ftp)(http) TXT
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Processed data are available on Series record
Raw data are available in SRA

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