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Series GSE66457 Query DataSets for GSE66457
Status Public on Jan 01, 2017
Title Mutational blows to Sox2+ cells induce epithelial squamous tumor initiation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cancer originates as the progressive accumulation of genetic mutations in proto-oncogenes and tumor suppressors. However, the early events underlying tumor initiation remain largely elusive, mostly due to the general lack of information regarding the cells-of-origin responsible for tumor formation as well as the precise impacts of genetic insults on tumor initiation in vivo. Here, we demonstrate that Sox2-positive (Sox2+) adult stem cells are responsible for epithelial squamous tumor formation. Conditional expression of oncogenic Kras (KrasG12D) and knockout of p53 (also known as Trp53) in Sox2+ cells quickly and specifically resulted in the formation of squamous tumors in the forestomach and esophagus. GFP-based lineage tracing experiments demonstrated that Sox2+ cells are the cells-of-origin of squamous tumors in the esophagus and forestomach. Of note, our data showed that p53 deletion alone did not suffice for tumor initiation. On the contrary, tumor initiation was observed upon KrasG12D activation whereas p53 deletion further contributed to the malignancy of the generated tumors, pointing out distinct roles for Kras activation and p53 deletion in squamous tumor formation and progression, to which a multihit carcinogenesis model can be applied. Global gene expression analysis revealed secreting factors upregulated in the generated tumors induced by oncogenic Kras, which contribute to tumor progression. Taken together, these results demonstrate that epithelial squamous tumors can specifically originate as a consequence of defined genetic mutations in a Sox2+ cell population and highlight the connections between proliferative stem cells and tumor development in vivo.
Overall design Expression profiling of mouse tissues with genetically induced tumors by RNA-Seq
Contributor(s) Hishida T, Benner C, Belmonte JC
Citation(s) 31041783
Submission date Mar 03, 2015
Last update date Jul 16, 2019
Contact name Christopher Benner
Organization name University of California, San Diego (UCSD)
Department Medicine
Street address 9500 Gilman Dr. MC 0640
City La Jolla
State/province California
ZIP/Postal code 92093-0640
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (12)
GSM1622721 Stomach_Sox2-CreER
GSM1622722 Stomach_Sox2-CreER, p53fl/+
GSM1622723 Stomach_Sox2-CreER, Kras
BioProject PRJNA277009
SRA SRP055753

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Supplementary file Size Download File type/resource
GSE66457_fpkm.txt.gz 2.3 Mb (ftp)(http) TXT
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Processed data are available on Series record
Raw data are available in SRA

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