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Series GSE266990 Query DataSets for GSE266990
Status Public on May 13, 2024
Title Haploinsufficient phenotypes promote selection of PTEN and ARID1A deficient clones in human colon.
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Normal human tissues are known to be composed of a pactchwork of mutant clones but with limited implications on cancer risk. PTEN and ARID1A deficient clones were detected in the human colon using immunohistrochemistry and were found to be the product of monoallelic loess. They were associated with a bias in clone dynamics which resulted in positive selection in the tissue. Heterozygous mutations were introduced in intestinal organoids which were subjected to bulk RNA-seq to describe the molecular mechanisms behind their positive selection. Although PTEN het organoids were associated with an advantageous phenotype in organoids, which was recapitulated in the transcriptomic analysis with increase proliferation and upregulation of developmental/regenerative processes and metabolic reprogramming, the ARID1A het organoids showed reduced growth which was seen as upregulation of apoptosis and downregulation of DNA replication. The discrepancy between the tissue and organoid phenotype for ARID1A was later explained due to the impact on stromal cells which are found in the tissue and are mediating the selective advantage. Importantly these molecular alterations and behaviours arise due to haploinsufficiency of these tumour suppressors in a pre-neoplastic context.
 
Overall design We subjected the generated heterozygous organoids to bulk RNA-seq to study the molecular effects of the monoallelic gene loss. PTEN het, ARID1A het, WT and PTEN KO- 4 replicates each that were different isogenic clones
 
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Submission date May 08, 2024
Last update date May 13, 2024
Contact name Nefeli Skoufou-Papoutsaki
E-mail(s) mns43@cam.ac.uk
Organization name University of Cambridge
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (16)
GSM8257801 WT_1
GSM8257802 PTEN_KO_4
GSM8257803 ARID1A_het_4
Relations
BioProject PRJNA1109299

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
GSE266990_allRawCounts.csv.gz 1.7 Mb (ftp)(http) CSV
GSE266990_normalizedCounts.csv.gz 3.7 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA

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