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Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer

ABSTRACT: Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer

PROVIDER: PRJNA830912 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18899400_1.fastq.gz	Fastqsanger.gz
	SRR18899400_2.fastq.gz	Fastqsanger.gz
	SRR18899401_1.fastq.gz	Fastqsanger.gz
	SRR18899401_2.fastq.gz	Fastqsanger.gz
	SRR18899402_1.fastq.gz	Fastqsanger.gz

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Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer [scRNA-seq]

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Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer [ATAC-seq]

Project description:Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer [ATAC-seq]

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Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer [scRNA-seq]

Project description:Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer [scRNA-seq]

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Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer.

Project description:To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.

| S-EPMC9279149 | biostudies-literature

Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-04-28 | GSE201349 | GEO

Gene expression analysis of microvesicular hyperplastic polyps and sessile serrated polyps/adenomas

Project description:In this study we compared gene expression of precancerous SSA/Ps and benign MVHPs with particular focus on genes involved in colorectal cancer. We also identify genes whose expression can be used to differentiate SSA/Ps and MVHPs. These results provide insight into the development of SSA/Ps and illustrates differences between these related colonic polyps. Total RNA from 6 samples of normal colon, 6 microvesicular hyperplastic polyps, and 6 sessile serrated adenomas/polyps were compared

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Transcriptome profiling across the cell wall expansion continuum in the Arabidopsis primary stem

Project description:Comparison of full-genome transcriptome profiles of four stages along the cell wall expansion continuum of the elongating inflorescence primary stem of Arabiopdis thaliana; plants ranging in height from 10-15cm.

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Time Lapse to Colorectal Cancer: Telomere Dynamics Define the Malignant Potential of Polyps.

Project description:ObjectiveWhereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free.MethodsTissues were identified as cancer-adjacent polyp (CAP)-residual adenoma contiguous with cancer-and cancer-free polyp (CFP)-adenomas without malignancy. Telomere length, TMM, and expression were measured in 102 tissues including peripheral blood leukocytes (PBLs), normal colon epithelium, adenoma, and cancer (in CAP cases) from 31 patients. Telomere length was measured in a separate cohort of 342 PBL from CAP and CFP patients.ResultsThe mean differences in telomere length between normal and adenoma were greater in CAP than in CFP cases, P=0.001; telomere length in PBL was 91.7 bp greater in CAP than in CFP, P=0.007. Each 100 bp telomere increase was associated with a 1.14 (1.04-1.26) increased odds of being a CAP, P=0.0063. The polyp tissue from CAP patients had shorter telomeres and higher Telomerase reverse transcriptase (hTERT) expression compared with polyps from CFP patients, P=0.05. There was a greater degree of alternative lengthening of telomere (ALT) level difference in CFP polyps than in CAP polyps. The polyp telomere lengths of aggressive CAPs were significantly different from the polyps of non-aggressive CAPs, P=0.01.ConclusionsAdenomas that progress to cancer exhibit distinct telomere length and TMM profiles. We report for the first time that PBL telomeres differ in patients with polyps that become malignant, and therefore may have clinical value in adenoma risk assessment and management.

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