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Series GSE222709 Query DataSets for GSE222709
Status Public on Feb 28, 2024
Title SOX17 initiates an immune evasion program in early colorectal cancers [RNAseq_200615Yil]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary In addition to accumulation of step-wise genetic mutations, epigenetic alterations play critical roles in the evolution of colon cancers. However, distinct mutational patterns and patient backgrounds render it challenging to distinguish driver epigenetic alterations from passenger epigenetic alterations. To address this, we combined the colon cancer organoid orthotopic transplantation approach with comprehensive epigenomic and transcriptomic analyses. We found that an in vivo environment induces epigenetic alterations with fetal intestinal features that converge on SOX17, a transcription factor that is required for endoderm development. Surprisingly, SOX17 knockout leads to tumour rejection in immunocompetent mice, but not in immunodeficient mice, by turning immune cold tumours into hot with robust infiltration of activated CD8+ T cells. Mechanistically, SOX17 suppresses Ifngr1-mediated MHC-I expression to evade CD8+ T cell-mediated tumour cell killing. At the tumour initiation, SOX17 expression is induced by APC loss, and SOX17 facilitates the production of LGR5- cells with low MHC-I expression to evade immune surveillance. Together, our result reveals that SOX17 is a master transcriptional factor that induces in vivo epigenetic reprograming of tumours, which provides fundamental understanding of how an immune evasion program is initiated at the early stages of colon cancer development.
Overall design We orthotopically transplanted naïve AKP organoids to immunocompetent and immunodeficient mice by colonoscopy, generated organoids from the primary tumours, and passaged several times until only cancer cells are present in the culture. In addition, to recapitulate the upregulation of SOX17 expression that occurs in vivo, we introduced dox-inducible and constitutive SOX17OE construct to the naïve AKP organoids by lentivirus transduction.
Contributor(s) Goto N, Goto S, Agudo J, Yilmaz O
Citation(s) 38418875
Submission date Jan 12, 2023
Last update date Apr 12, 2024
Contact name Norihiro Goto
Organization name Massachusetts Institute of Technology
Department Department of Biology
Lab Yilmaz lab
Street address 500 Main Street, Building 76
City Cambridge
State/province MA
ZIP/Postal code 02139-4307
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (11)
GSM6929233 Naïve_AKP_replicate1 [Naive_1 RNA-seq]
GSM6929234 Naïve_AKP_replicate2 [Naive_2 RNA-seq]
GSM6929235 Naïve_AKP_replicate3 [Naive_3 RNA-seq]
This SubSeries is part of SuperSeries:
GSE222713 SOX17 initiates an immune evasion program in early colorectal cancers.
BioProject PRJNA923247

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

Supplementary file Size Download File type/resource
GSE222709_ngoto_200615Yil_Ct.txt.gz 459.7 Kb (ftp)(http) TXT
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Processed data are available on Series record

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