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Series GSE133514 Query DataSets for GSE133514
Status Public on Jun 19, 2021
Title Defining AP4-regulated gene expression programs in pro/pre-B cells overexpressing c-MYC
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary A hallmark feature of adaptive immune cells is their capacity for rapid cell proliferation required for producing and expanding cells with a diverse repertoire of antigen receptor and amplification of antigen-specific receptors. While proliferation is beneficial for host protection from infection and cancers, it inevitably elevates the risk of oncogenic transformation. Developing lymphocytes, as well as B cells in the germinal center (GC), are considered tumor-prone due to additional genomic insults from physiological antigen receptor gene rearrangement and editing. However, oncogenic transformation of lymphocytes is relatively rare, perhaps owing to an intrinsic, tumor-suppressive program. Here, we show that c-MYC not only facilitates rapid cell proliferation but, unexpectedly, also engages a counteracting tumor suppressive program through its downstream transcription factor, AP4. Haploinsufficiency for AP4 dramatically accelerates MYC-driven tumorigenesis in a B cell-intrinsic manner. At a mechanistic level, AP4 suppresses Erg, which is required for B cell development but also oncogenic, in MYC+ developing B cells, and thus AP4 restricts simultaneous expression of multiple oncogenic factors during B cell development. Thus, c-MYC has dual action that permit proliferative expansion of B cell precursors, while concurrently safeguarding against their transformation via engagement of an AP4-dependent, tumor-suppressive program.
Overall design B220+IgM– pro/pre B cells from EuMyc or EuMyc Tfap4 heterozygous mice were isolated at 3-4 weeks of age, prior to tumor development, or from developed tumors and gene expression, AP4 occupancy, and H3K27ac deposition was analyzed with n=2-5 biological replicates.
Contributor(s) Egawa T
Citation(s) 34283887
Submission date Jun 28, 2019
Last update date Aug 08, 2021
Contact name Takeshi Egawa
Organization name Washington University School of Medicine
Department Pathology and Immunology
Street address 660 South Euclid
City Saint Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (47)
GSM3911164 7072 RNA_seq
GSM3911165 7074 RNA_seq
GSM3911166 7076 RNA_seq
BioProject PRJNA551667
SRA SRP212619

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Supplementary file Size Download File type/resource
GSE133514_RAW.tar 631.8 Mb (http)(custom) TAR (of BEDGRAPH)
GSE133514_all.gene_RPKM_Tonc_etal.xlsx 13.1 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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