title: Comprehensive site-specific whole genome profiling of stromal and epithelial colonic gene signatures in human sigmoid colon and rectal tissue.
abstract: The strength of associations between various exposures (e.g., diet, tobacco, chemopreventive agents) and colorectal cancer risk may partially depend on the complex interaction between epithelium and stroma across anatomic subsites. Currently, baseline data describing genome-wide coding and long noncoding gene expression profiles in the healthy colon specific to tissue type and location are lacking. Therefore, colonic mucosal biopsies from 10 healthy participants who were enrolled in a clinical study to evaluate effects of lignan supplementation on gut resiliency were used to characterize the site-specific global gene expression signatures associated with stromal vs. epithelial cells in the sigmoid colon and rectum. Using RNA-seq, we demonstrate that tissue type and location patterns of gene expression and upstream regulatory pathways are distinct. For example, consistent with a key role of stroma in the crypt niche, mRNAs associated with immunoregulatory and inflammatory processes (i.e., CXCL14, ANTXR1), smooth muscle contraction (CALD1), proliferation and apoptosis (GLP2R, IGFBP3), and modulation of extracellular matrix (MMP2, COL3A1, MFAP4) were all highly expressed in the stroma. In comparison, HOX genes (HOXA3, HOXD9, HOXD10, HOXD11, and HOXD-AS2, a HOXD cluster antisense RNA 2), and WNT5B expression were also significantly higher in sigmoid colon compared with the rectum. These findings provide strong impetus for considering colorectal tissue subtypes and location in future observational studies and clinical trials designed to evaluate the effects of exposures on colonic health.
authors.affiliation: Department of Electrical Engineering, Texas A&M University, College Station, Texas; Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas;
authors.forename: Jason M
authors.initials: JM
authors.lastname: Knight
authors.affiliation: Department of Electrical Engineering, Texas A&M University, College Station, Texas; Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas;
authors.forename: Eunji
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station, Texas; Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas;
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivanov
authors.affiliation: Department of Nutrition & Food Science, Texas A&M University, College Station, Texas; Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas;
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Davidson
authors.affiliation: Department of Nutrition & Food Science, Texas A&M University, College Station, Texas; Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas;
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Goldsby
authors.affiliation: Fred Hutchinson Cancer Research Center, Texas A&M University, College Station, Texas; and.
authors.forename: Meredith A J
authors.initials: MA
authors.lastname: Hullar
authors.affiliation: Fred Hutchinson Cancer Research Center, Texas A&M University, College Station, Texas; and.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Randolph
authors.affiliation: Fred Hutchinson Cancer Research Center, Texas A&M University, College Station, Texas; and Gastroenterology Section, VA Puget Sound Medical Center, Seattle, Washington.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Kaz
authors.affiliation: Fred Hutchinson Cancer Research Center, Texas A&M University, College Station, Texas; and.
authors.forename: Lisa
authors.initials: L
authors.lastname: Levy
authors.affiliation: Fred Hutchinson Cancer Research Center, Texas A&M University, College Station, Texas; and.
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.affiliation: Department of Nutrition & Food Science, Texas A&M University, College Station, Texas; Center for Translational Environmental Health Research, Texas A&M University, College Station, Texas; r-chapkin@tamu.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Chapkin
mesh_terms: D000328:Adult; D001706:Biopsy; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012809:Colon, Sigmoid / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017705:Lignans / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012007:Rectum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: D017705:Lignans; D012333:RNA, Messenger
keywords: HOX genes; epithelium; human colon; long noncoding RNA; stroma