GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE90918 Query DataSets for GSE90918
Status Public on Aug 01, 2017
Title Blimp1 induces transient metastatic heterogeneity in pancreatic cancer [688M_ATAC-seq]
Organism Mus musculus
Experiment type Other
Summary Purpose: Due to its high metastatic proclivity, pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly types of cancer. Therefore, it is imperative to better understand how the disease spreads as it progresses. Using a novel genetically engineered mouse model that allows us to isolate a subpopulation of cancer cells with superior metastatic capacity, we show that this aggressive phenotype correlates exclusively with a strong hypoxia signature. We subsequently identified the novel hypoxia-inducible gene Blimp1, which appears to play a critical role in regulating the hypoxic response upon its induction. Furthermore, genetic ablation of Blimp1 greatly reduces the level of metastasis in a PDAC mouse model. The nature of this Blimp1-regulated hypoxia signature is very unstable, since the seeded metastatic lesions mostly re-adopt similar transcriptomic profiles as the primary tumors. In conclusion, our results offer a potential mechanistic insight into how hypoxia drives metastasis in PDAC.
Methods: The liver metastasis cell line 688M was subjected to control or knockdown of Blimp1 before assay. Cells ere validated for knockdown efficiency and then cultured under normoxia and hypoxia (0.5% O2) for 24 hours before preparation for ATAC-Seq (total of 4 groups with 2 technical replicates per group, overall 8 samples). Reference for ATACSeq: Buenrostro et al. 2013. Nat Methods 12:1213-8.
Results: For the control knockdown group, 0.5% O2 culture (hypoxia) for 24 hours induced dramatic changes in global genome accessibility, and Blimp1 knockdown appeared to induce minimum changes in chromatin accessibility under hypoxia or normoxia (20% O2).
Conclusions: Compared to our RNASeq profiles of the same liver met PDAC cell line under identical conditions, Blimp1 appeared to impact a global gene expression changes under hypoxia that is not associated with a corresponding changes of chromatin accessibility.
Overall design Transcriptomes of derivatives of liver metastasis cell line 688M (control and Blimp1 knockdown) derived from the KPCT (Kras-LSL-G12D;p53-LSL-R172H;Pdx1-cre;R26-LSL-Tomato) mice were cultured under 0.5% or 20% O2 for 24 hours before ATAC-Seq preparation (Illumina NextSeq).
Web link
Contributor(s) Winslow M, Chiou S
Citation(s) 28790031
Submission date Dec 05, 2016
Last update date May 15, 2019
Contact name Shin-Heng Chiou
Organization name Stanford University
Department Genetics
Street address 450 Serra Mall
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (8)
GSM2417499 Hypoxia control KD ATAC-seq rep1
GSM2417500 Hypoxia control KD ATAC-seq rep2
GSM2417501 Hypoxia Blimp1 KD ATAC-seq rep1
This SubSeries is part of SuperSeries:
GSE90825 Blimp1 induces transient metastatic heterogeneity in pancreatic cancer
BioProject PRJNA356320
SRA SRP094594

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
GSE90918_ATACSeq_peaks_and_inserts_SC.txt.gz 1.8 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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