NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE221298 Query DataSets for GSE221298
Status Public on Apr 03, 2023
Title Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation [ATAC-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Cell state (phenotypic) plasticity is a carefully regulated feature of adult epithelial cells that enables adaptive responses to injury, inflammation, and other forms of stress.Aberrant expansion of the normally restricted capability for cell state plasticity to escape terminal differentiation is a critical aspect of neoplasia. The nongenetic factors and specific programs that mediate aberrant cell state plasticity and impaired differentiationrequire deeper characterization to understand this elusive aspect ofcancer pathogenesis. Using genetically engineered andcarcinogen-induced murine models of intestinal neoplasia, wedemonstrate that impaired differentiation is a conserved eventpreceding cancer development. Single cell RNA-sequencing (scRNA-seq)of neoplastic intestinal lesions from both mouse models and a patientwith familial adenomatous polyposis revealed that cancer initiates byadopting an aberrant transcriptional state characterized bynonoverlapping expression of a regenerative pathway, marked by Ly6a(Sca-1), and a fetal intestinal program, positive for Tacstd2 (Trop2).Genetic inactivation of Sox9 prevented adenoma formation in ApcKOmice, obstructed emergence of aberrant regenerative and fetalintestinal programs, and restored multi-lineage differentiation byscRNA-seq. Expanded chromatin accessibility at regeneration and fetalgenes upon Apc inactivation was reduced by concomitant Sox9suppression. These studies indicate that aberrant cell stateplasticity mediated by unabated regenerative activity anddevelopmental reprogramming precedes cancer development.
 
Overall design ATAC-seq
 
Contributor(s) Bala P, Aitymbayev D, Rennhack J, Li Z, Sethi N
Citation(s) 36989360
Submission date Dec 19, 2022
Last update date Apr 04, 2023
Contact name Nilay Sethi
E-mail(s) nilay_sethi@dfci.harvard.edu
Organization name DANA-FARBER CANCER INSTITUTE
Street address 450 Brookline Ave
City BOSTON
State/province Massachusetts
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM6857972 Lgr5-Apcf/f-tdT rep1
GSM6857973 Lgr5-Apcf/f-tdT rep2
GSM6857974 Lgr5-Apcf/f-Sox9f/+-tdT rep1
This SubSeries is part of SuperSeries:
GSE221300 Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation
Relations
BioProject PRJNA913874

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
GSE221298_RAW.tar 2.7 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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