NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
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
E-mail(s) tegawa@wustl.edu
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
Relations
BioProject PRJNA551667
SRA SRP212619

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap