Transcriptomics

Dataset Information

298

RNA sequencing expression analysis of murine MLL-AF9;NRAS acute myeloid leukemia cells silenced for E2-2.


ABSTRACT: We investigated the role of the transcriptional regulators Id2 and E2-2 (encoded by Tcf4) in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by a Tet-off inducible MLL-AF9 allele co-expressed with oncogenic NRASG12D, 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 MLL-AF9 AML cells results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. E2-2 silencing phenocopies Id2 overexpression in MLL-AF9-AML cells. To study the gene expression changes associated with E2-2 depletion in the context of MLL-rearranged AML, RNA sequencing analysis was performed on MLL-AF9;NRAS AML cells transduced with vectors expressing hairpins against E2-2 (shTcf4#654 and shTcf4#3646) or a control hairpin against Renilla luciferase (shRen). Primary AMLs driven by MLL/AF9 expression linked to cherry reporter, in association with oncogenic NRASG12D (MLL/AF9;NRAS) were generated by reconstituting lethally irradiated congenic mice with fetal liver cells co-transduced with the MSCV-MLL/AF9-IRES-cherry retroviral vector and a second vector co-expressing NRASG12D together with luciferase (MSCV-luciferase-IRES-NRASG12D). RNA sequencing analysis sequencing analysis was performed on MLL-AF9;NRAS AML cells transduced in vitro with vectors expressing hairpins against E2-2 (shTcf4#654 and shTcf4#3646) or a control hairpin against Renilla luciferase (shRen) linked to the reporter GFP. Viable GFP-positive cells were FACS-sorted 2 days after transduction and used for RNA sequencing analysis. Two independent biological replicates of the experiment were used for the RNA sequencing (9-5-14 and 14-4-14).

ORGANISM(S): Mus musculus  

SUBMITTER: Frederic Masson   Lev Kats  Margherita Ghisi  Kirsten A Fairfax  Ricky W Johnstone  Ross A Dickins  Carolyn A de Graaf  Tobias Kratina  Jessica E Bolden  Lynn M Corcoran  Mark A Dawson  Eva Vidacs  Matthew Firth  Maria A Doyle  Omer Gilan  Jason Li  Andrea Newbold  Johannes Zuber  Gabrielle T Belz 

PROVIDER: E-GEOD-80745 | ArrayExpress | 2016-06-29

SECONDARY ACCESSION(S): GSE80745SRP074101PRJNA319906

REPOSITORIES: GEO, ArrayExpress, ENA

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