Mapping the Human Colon Using Single Cell Sequencing

NCT ID: NCT05195502

Last Updated: 2023-02-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-07-01

Study Completion Date

2024-07-01

Brief Summary

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The overall purpose of this study is to describe the cellular composition of the human colon and its gene expression using scRNAseq and scATACseq methods. This will potentially provide is with a detailed map of the colon aiding our understanding of how diseases of the colon develop as well as the colons influence on systemic diseases such as type II diabetes.

Detailed Description

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The human colon is composed of four distinct histological layers: Serosa, muscularis externa, submucosa, and mucosa. The inner mucosal surface is composed of columnar epithelium and glandular tissue containing crypts of Lieberkühn and secretory goblet cells, lamina propria and muscularis mucosa. Several distinct cell types have been discovered in varying degree in the colon for example enteroendocrine cells and M-cells.

The cellular composition, patterns of gene expression and upstream regulatory pathways of the human colon varies across different anatomical location. This is evident in the anatomical bias in benign and malignant colorectal diseases. For example, the distal colon has a higher incidens of ulcerative colitis, diverticulitis, and chromosomal instability cancer whereas in the proximal colon ischemic colitis, collagenous colitis and microsatellite instability-induced cancer are predominant.

Currently there are no studies describing baseline data for genome-wide coding, methylation or gene expression related to specific anatomic locations in the human colon.

By using scRNAseq and scATACseq (Single-cell Assay of Transposase Accessible Chromatin sequencing) we will be able to map open regions in the cell's DNA and RNA, thus providing us with a unique "map" of the cells in the colon as well is their gene expression. ScATACseq visualizes open regions in the chromatin, generating "peaks" which can then be used to map DNA motifs, such as transcription factor binding sites. With the emergence of scATACseq, chromatin accessibility is in combination with gene expression data an extremely useful resource to study cell type specific regulatory DNA interactions. To further study the immunological aspects of the colon, we will extract immune cells from the colon. Lastly, full blood will be extracted to better analyze metabolic risk factors in relation to the colon's metabolic cellular regulation.

The overall purpose of this study is to describe the cellular composition of the human colon and its gene expression using scRNAseq and scATACseq methods. This will potentially provide is with a detailed map of the colon aiding our understanding of how diseases of the colon develop as well as the colons influence on systemic diseases such as type II diabetes.

Conditions

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Diabetes Large Bowel Cancer Inflammatory Bowel Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Screening colonoscopy patients

Patients referred for out-patient colonoscopy in the Danish Colorectal Screening program

Biopsy

Intervention Type DIAGNOSTIC_TEST

Participants included in the study, will have additional biopsies performed during their colonoscopy

Interventions

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Biopsy

Participants included in the study, will have additional biopsies performed during their colonoscopy

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients referred for out-patient colonoscopy as a result of positive hemoccult.
* Patients able to read and understand danish.
* Patients able to give informed consent.
* Patients of Scandinavian ethnicity.

Exclusion Criteria

* Previous large bowel resections
* Suspicion pre or intraoperatively of benign or malignant disease of the colon
* Known inflammatory bowel disease.
* Immuno-modulation treatment
* Chemotherapy.
* Daily smoking
* \> 21 weekly units of alcohol
* \< 18 years of age
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Novo Nordisk Foundation Center for Basic Metabolic Research

OTHER

Sponsor Role collaborator

Bispebjerg Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jacob Antonsen

Senior Registrar

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jacob Antonsen, MD

Role: PRINCIPAL_INVESTIGATOR

Bispebjerg Hospital

Locations

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Bispebjerg University Hospital

Copenhagen, , Denmark

Site Status

Countries

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Denmark

References

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Kaz AM, Wong CJ, Dzieciatkowski S, Luo Y, Schoen RE, Grady WM. Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age. Epigenetics. 2014 Apr;9(4):492-502. doi: 10.4161/epi.27650. Epub 2014 Jan 10.

Reference Type BACKGROUND
PMID: 24413027 (View on PubMed)

Knight JM, Kim E, Ivanov I, Davidson LA, Goldsby JS, Hullar MA, Randolph TW, Kaz AM, Levy L, Lampe JW, Chapkin RS. Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue. Physiol Genomics. 2016 Sep 1;48(9):651-9. doi: 10.1152/physiolgenomics.00023.2016. Epub 2016 Jul 8.

Reference Type BACKGROUND
PMID: 27401218 (View on PubMed)

Forgue-Lafitte ME, Fabiani B, Levy PP, Maurin N, Flejou JF, Bara J. Abnormal expression of M1/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancer. Int J Cancer. 2007 Oct 1;121(7):1543-9. doi: 10.1002/ijc.22865.

Reference Type BACKGROUND
PMID: 17565737 (View on PubMed)

Costales-Carrera A, Fernandez-Barral A, Bustamante-Madrid P, Dominguez O, Guerra-Pastrian L, Cantero R, Del Peso L, Burgos A, Barbachano A, Munoz A. Comparative Study of Organoids from Patient-Derived Normal and Tumor Colon and Rectal Tissue. Cancers (Basel). 2020 Aug 15;12(8):2302. doi: 10.3390/cancers12082302.

Reference Type BACKGROUND
PMID: 32824266 (View on PubMed)

Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide. Curr Protoc Mol Biol. 2015 Jan 5;109:21.29.1-21.29.9. doi: 10.1002/0471142727.mb2129s109.

Reference Type BACKGROUND
PMID: 25559105 (View on PubMed)

Other Identifiers

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COLKEND01

Identifier Type: -

Identifier Source: org_study_id

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