Modeling the effect of prolonged ethanol exposure on global gene expression and chromatin accessibility in normal 3D colon organoids.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
12
07
2019
accepted:
11
12
2019
entrez:
18
1
2020
pubmed:
18
1
2020
medline:
9
4
2020
Statut:
epublish
Résumé
In this study we aimed to explore the potential biological effect of ethanol exposure on healthy colon epithelial cells using normal human colon 3D organoid "mini-gut" cultures. In numerous published studies ethanol use has been shown to be an environmental risk factor for colorectal cancer (CRC) development; however, the influence of ethanol exposure on normal colon epithelial cell biology remains poorly understood. We investigated the potential molecular effects of ethanol exposure in normal colon 3D organoids in a small pilot study (n = 3) using RNA-seq and ATAC-seq. We identify 1965 differentially expressed genes and 2217 differentially accessible regions of chromatin in response to ethanol treatment. Further, by cross-referencing our results with previously published analysis in colorectal cancer cell lines, we have not only validated a number of reported differentially expressed genes, but also identified several novel candidates for future investigation. In summary, our data highlights the potential importance for the use of normal colon 3D organoid models as a novel tool for the investigation of the relationship between the effects of environmental risk factors associated with colorectal cancer and the molecular mechanisms through which they confer this risk.
Identifiants
pubmed: 31951625
doi: 10.1371/journal.pone.0227116
pii: PONE-D-19-19903
pmc: PMC6968849
doi:
Substances chimiques
Chromatin
0
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0227116Subventions
Organisme : NCI NIH HHS
ID : R01 CA143237
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201407
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nature. 2016 Mar 3;531(7592):53-8
pubmed: 26935695
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Mod Pathol. 2019 Jan;32(Suppl 1):1-15
pubmed: 30600322
Nature. 2009 May 14;459(7244):262-5
pubmed: 19329995
Cell. 2016 Jun 16;165(7):1586-1597
pubmed: 27315476
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell. 2008 May 2;133(3):523-36
pubmed: 18423832
Mol Metab. 2016 Jan 11;5(3):233-244
pubmed: 26977395
Nat Commun. 2018 Apr 10;9(1):1364
pubmed: 29636475
Development. 2018 Mar 14;145(6):
pubmed: 29467240
Alcohol Clin Exp Res. 2017 Dec;41(12):2100-2113
pubmed: 28992396
PLoS Comput Biol. 2017 Nov 3;13(11):e1005752
pubmed: 29099853
Nat Methods. 2013 Dec;10(12):1213-8
pubmed: 24097267
Cell Stem Cell. 2018 Dec 6;23(6):787-793.e6
pubmed: 30526881
Nature. 2018 Apr;556(7702):457-462
pubmed: 29643510
World J Gastroenterol. 2014 May 28;20(20):6055-72
pubmed: 24876728
BMC Cancer. 2014 May 28;14:377
pubmed: 24886599
Nat Rev Genet. 2016 May;17(5):257-71
pubmed: 26996076
Mol Syst Biol. 2018 Jun 26;14(6):e8227
pubmed: 29945941
Nat Genet. 2019 Jan;51(1):76-87
pubmed: 30510241
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Lancet. 2015 Mar 14;385(9972):977-1010
pubmed: 25467588
Breast Cancer Res Treat. 2012 Jun;133(3):1037-48
pubmed: 22160640
Alcohol Clin Exp Res. 2010 Jan;34(1):19-31
pubmed: 19860811
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Science. 2018 Sep 28;361(6409):1380-1385
pubmed: 30166440
Nat Methods. 2017 Oct;14(10):959-962
pubmed: 28846090
J Clin Pathol. 2019 Feb;72(2):135-139
pubmed: 30425122
J Biol Chem. 2014 Mar 7;289(10):6839-49
pubmed: 24443565
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11
pubmed: 19465376