Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis
Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic a...
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| Veröffentlicht in: | Clinical epigenetics 2020-12, Vol.12 (1), p.190, Article 190 |
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| creator | Good, Misty Chu, Tianjiao Shaw, Patricia McClain, Lora Chamberlain, Austin Castro, Carlos Rimer, Jamie M Mihi, Belgacem Gong, Qingqing Nolan, Lila S Cooksey, Krista Linneman, Laura Agrawal, Pranjal Finegold, David N Peters, David |
| description | Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.
Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data.
We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation.
We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping. |
| doi_str_mv | 10.1186/s13148-020-00983-6 |
| format | Article |
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Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data.
We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation.
We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.</description><identifier>ISSN: 1868-7075</identifier><identifier>ISSN: 1868-7083</identifier><identifier>EISSN: 1868-7083</identifier><identifier>EISSN: 1868-7075</identifier><identifier>DOI: 10.1186/s13148-020-00983-6</identifier><identifier>PMID: 33308304</identifier><language>eng</language><publisher>Germany: BioMed Central Ltd</publisher><subject>Analysis ; Animals ; Bisulfite ; Case-Control Studies ; Colon ; Colon - pathology ; Colon - surgery ; CpG Islands - genetics ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Enterocolitis ; Enterocolitis, Necrotizing - etiology ; Enterocolitis, Necrotizing - genetics ; Enterocolitis, Necrotizing - pathology ; Enterocolitis, Necrotizing - surgery ; Enterocolitis, Neonatal necrotizing ; Enterocolitis, Pseudomembranous ; Epigenetic inheritance ; Epigenomics - methods ; Epithelial cells ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Gastrointestinal diseases ; Gene expression ; Genes ; Genetic testing ; Genetic transcription ; Genome-Wide Association Study - methods ; Genomes ; Genomics ; Genotype & phenotype ; Humans ; Ileum ; Ileum - pathology ; Ileum - surgery ; Infant, Newborn ; Infants ; Infants (Premature) ; Intestine ; Intestines - pathology ; Laser Capture Microdissection - adverse effects ; Laser Capture Microdissection - methods ; Methylation ; Models, Animal ; Necrosis ; Necrotizing enterocolitis ; Neonates ; Pathogenesis ; Phenotypes ; Phenotyping ; Precision medicine ; Premature birth ; Ribonucleic acid ; RNA ; RNA sequencing ; Sequence Analysis, RNA - methods ; Sulfites ; Surgery ; Transcription ; Transcriptome - genetics ; Transcriptomics</subject><ispartof>Clinical epigenetics, 2020-12, Vol.12 (1), p.190, Article 190</ispartof><rights>COPYRIGHT 2020 BioMed Central Ltd.</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-ba2b664d84159651cca87c2b55b04a6737b728d805355063905f95d03d86a3a83</citedby><cites>FETCH-LOGICAL-c497t-ba2b664d84159651cca87c2b55b04a6737b728d805355063905f95d03d86a3a83</cites><orcidid>0000-0002-0264-5721</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730811/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730811/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33308304$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Good, Misty</creatorcontrib><creatorcontrib>Chu, Tianjiao</creatorcontrib><creatorcontrib>Shaw, Patricia</creatorcontrib><creatorcontrib>McClain, Lora</creatorcontrib><creatorcontrib>Chamberlain, Austin</creatorcontrib><creatorcontrib>Castro, Carlos</creatorcontrib><creatorcontrib>Rimer, Jamie M</creatorcontrib><creatorcontrib>Mihi, Belgacem</creatorcontrib><creatorcontrib>Gong, Qingqing</creatorcontrib><creatorcontrib>Nolan, Lila S</creatorcontrib><creatorcontrib>Cooksey, Krista</creatorcontrib><creatorcontrib>Linneman, Laura</creatorcontrib><creatorcontrib>Agrawal, Pranjal</creatorcontrib><creatorcontrib>Finegold, David N</creatorcontrib><creatorcontrib>Peters, David</creatorcontrib><title>Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis</title><title>Clinical epigenetics</title><addtitle>Clin Epigenetics</addtitle><description>Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.
Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data.
We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation.
We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.</description><subject>Analysis</subject><subject>Animals</subject><subject>Bisulfite</subject><subject>Case-Control Studies</subject><subject>Colon</subject><subject>Colon - pathology</subject><subject>Colon - surgery</subject><subject>CpG Islands - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Enterocolitis</subject><subject>Enterocolitis, Necrotizing - etiology</subject><subject>Enterocolitis, Necrotizing - genetics</subject><subject>Enterocolitis, Necrotizing - pathology</subject><subject>Enterocolitis, Necrotizing - surgery</subject><subject>Enterocolitis, Neonatal necrotizing</subject><subject>Enterocolitis, Pseudomembranous</subject><subject>Epigenetic inheritance</subject><subject>Epigenomics - methods</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Gastrointestinal diseases</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic testing</subject><subject>Genetic transcription</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Ileum</subject><subject>Ileum - pathology</subject><subject>Ileum - surgery</subject><subject>Infant, Newborn</subject><subject>Infants</subject><subject>Infants (Premature)</subject><subject>Intestine</subject><subject>Intestines - pathology</subject><subject>Laser Capture Microdissection - adverse effects</subject><subject>Laser Capture Microdissection - methods</subject><subject>Methylation</subject><subject>Models, Animal</subject><subject>Necrosis</subject><subject>Necrotizing enterocolitis</subject><subject>Neonates</subject><subject>Pathogenesis</subject><subject>Phenotypes</subject><subject>Phenotyping</subject><subject>Precision medicine</subject><subject>Premature birth</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>Sequence Analysis, RNA - methods</subject><subject>Sulfites</subject><subject>Surgery</subject><subject>Transcription</subject><subject>Transcriptome - genetics</subject><subject>Transcriptomics</subject><issn>1868-7075</issn><issn>1868-7083</issn><issn>1868-7083</issn><issn>1868-7075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptUk1v1DAUjBAVrUr_QA8oEhcuKXb8mQtSVUFBqsSFni3HcTYujr3YDtKWP89Lt10owjn4KW9m_N5oquocowuMJX-fMcFUNqhFDUKdJA1_UZ1AQzYCSfLyUAt2XJ3lfIfgkK7rMHpVHRNCAIToSfXr2sde-3rabW2abZl2XhcXQx3H2oVic3EB2nbrymS9g9JY73Ptcq3rSXs_6_S9Hq0uS7IrKdgYdAFcXtLGGSiCNSkWd-_CprYgmaKJ3hWXX1dHo_bZnj3ep9Xtp4_frj43N1-vv1xd3jSGdqI0vW57zukgKWYdZ9gYLYVpe8Z6RDUXRPSilYNEjDCGOOkQGzs2IDJIromW5LT6sNfdLv1sBwNDJO3VNjkYfqeidup5J7hJbeJPJQTYhDEIvHsUSPHHAp6o2eXVBw3bLlm1VIC5MAgB6Nt_oHdxSWDhAwq3SCDG_6A22lvlwhjhXbOKqktOYRPe0g5QF_9BwTfY2ZkY7Ojg_zNCuyeA4TknOx52xEitqVH71ChIjXpIjVpnefO3OwfKU0bIb6NvveY</recordid><startdate>20201211</startdate><enddate>20201211</enddate><creator>Good, Misty</creator><creator>Chu, Tianjiao</creator><creator>Shaw, Patricia</creator><creator>McClain, Lora</creator><creator>Chamberlain, Austin</creator><creator>Castro, Carlos</creator><creator>Rimer, Jamie M</creator><creator>Mihi, Belgacem</creator><creator>Gong, Qingqing</creator><creator>Nolan, Lila S</creator><creator>Cooksey, Krista</creator><creator>Linneman, Laura</creator><creator>Agrawal, Pranjal</creator><creator>Finegold, David N</creator><creator>Peters, David</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0264-5721</orcidid></search><sort><creationdate>20201211</creationdate><title>Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis</title><author>Good, Misty ; Chu, Tianjiao ; Shaw, Patricia ; McClain, Lora ; Chamberlain, Austin ; Castro, Carlos ; Rimer, Jamie M ; Mihi, Belgacem ; Gong, Qingqing ; Nolan, Lila S ; Cooksey, Krista ; Linneman, Laura ; Agrawal, Pranjal ; Finegold, David N ; Peters, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-ba2b664d84159651cca87c2b55b04a6737b728d805355063905f95d03d86a3a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Bisulfite</topic><topic>Case-Control Studies</topic><topic>Colon</topic><topic>Colon - pathology</topic><topic>Colon - surgery</topic><topic>CpG Islands - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Enterocolitis</topic><topic>Enterocolitis, Necrotizing - etiology</topic><topic>Enterocolitis, Necrotizing - genetics</topic><topic>Enterocolitis, Necrotizing - pathology</topic><topic>Enterocolitis, Necrotizing - surgery</topic><topic>Enterocolitis, Neonatal necrotizing</topic><topic>Enterocolitis, Pseudomembranous</topic><topic>Epigenetic inheritance</topic><topic>Epigenomics - methods</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Gastrointestinal diseases</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic testing</topic><topic>Genetic transcription</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype & phenotype</topic><topic>Humans</topic><topic>Ileum</topic><topic>Ileum - pathology</topic><topic>Ileum - surgery</topic><topic>Infant, Newborn</topic><topic>Infants</topic><topic>Infants (Premature)</topic><topic>Intestine</topic><topic>Intestines - pathology</topic><topic>Laser Capture Microdissection - adverse effects</topic><topic>Laser Capture Microdissection - methods</topic><topic>Methylation</topic><topic>Models, Animal</topic><topic>Necrosis</topic><topic>Necrotizing enterocolitis</topic><topic>Neonates</topic><topic>Pathogenesis</topic><topic>Phenotypes</topic><topic>Phenotyping</topic><topic>Precision medicine</topic><topic>Premature birth</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>Sequence Analysis, RNA - methods</topic><topic>Sulfites</topic><topic>Surgery</topic><topic>Transcription</topic><topic>Transcriptome - genetics</topic><topic>Transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Good, Misty</creatorcontrib><creatorcontrib>Chu, Tianjiao</creatorcontrib><creatorcontrib>Shaw, Patricia</creatorcontrib><creatorcontrib>McClain, Lora</creatorcontrib><creatorcontrib>Chamberlain, Austin</creatorcontrib><creatorcontrib>Castro, Carlos</creatorcontrib><creatorcontrib>Rimer, Jamie M</creatorcontrib><creatorcontrib>Mihi, Belgacem</creatorcontrib><creatorcontrib>Gong, Qingqing</creatorcontrib><creatorcontrib>Nolan, Lila S</creatorcontrib><creatorcontrib>Cooksey, Krista</creatorcontrib><creatorcontrib>Linneman, Laura</creatorcontrib><creatorcontrib>Agrawal, Pranjal</creatorcontrib><creatorcontrib>Finegold, David N</creatorcontrib><creatorcontrib>Peters, David</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical epigenetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Good, Misty</au><au>Chu, Tianjiao</au><au>Shaw, Patricia</au><au>McClain, Lora</au><au>Chamberlain, Austin</au><au>Castro, Carlos</au><au>Rimer, Jamie M</au><au>Mihi, Belgacem</au><au>Gong, Qingqing</au><au>Nolan, Lila S</au><au>Cooksey, Krista</au><au>Linneman, Laura</au><au>Agrawal, Pranjal</au><au>Finegold, David N</au><au>Peters, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis</atitle><jtitle>Clinical epigenetics</jtitle><addtitle>Clin Epigenetics</addtitle><date>2020-12-11</date><risdate>2020</risdate><volume>12</volume><issue>1</issue><spage>190</spage><pages>190-</pages><artnum>190</artnum><issn>1868-7075</issn><issn>1868-7083</issn><eissn>1868-7083</eissn><eissn>1868-7075</eissn><abstract>Necrotizing enterocolitis (NEC) remains one of the overall leading causes of death in premature infants, and the pathogenesis is unpredictable and not well characterized. The aim of our study was to determine the molecular phenotype of NEC via transcriptomic and epithelial cell-specific epigenomic analysis, with a specific focus on DNA methylation.
Using laser capture microdissection, epithelial cell-specific methylation signatures were characterized by whole-genome bisulfite sequencing of ileal and colonic samples at the time of surgery for NEC and after NEC had healed at reanastomosis (n = 40). RNA sequencing was also performed to determine the transcriptomic profile of these samples, and a comparison was made to the methylome data.
We found that surgical NEC has a considerable impact on the epigenome by broadly increasing DNA methylation levels, although these effects are less pronounced in genomic regions associated with the regulation of gene expression. Furthermore, NEC-related DNA methylation signatures were influenced by tissue of origin, with significant differences being noted between colon and ileum. We also identified numerous transcriptional changes in NEC and clear associations between gene expression and DNA methylation.
We have defined the intestinal epigenomic and transcriptomic signatures during surgical NEC, which will advance our understanding of disease pathogenesis and may enable the development of novel precision medicine approaches for NEC prediction, diagnosis and phenotyping.</abstract><cop>Germany</cop><pub>BioMed Central Ltd</pub><pmid>33308304</pmid><doi>10.1186/s13148-020-00983-6</doi><orcidid>https://orcid.org/0000-0002-0264-5721</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical epigenetics, 2020-12, Vol.12 (1), p.190, Article 190 |
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| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Springer Nature OA Free Journals; Springer Nature - Complete Springer Journals; PubMed Central |
| subjects | Analysis Animals Bisulfite Case-Control Studies Colon Colon - pathology Colon - surgery CpG Islands - genetics Deoxyribonucleic acid DNA DNA Methylation Enterocolitis Enterocolitis, Necrotizing - etiology Enterocolitis, Necrotizing - genetics Enterocolitis, Necrotizing - pathology Enterocolitis, Necrotizing - surgery Enterocolitis, Neonatal necrotizing Enterocolitis, Pseudomembranous Epigenetic inheritance Epigenomics - methods Epithelial cells Epithelial Cells - metabolism Epithelial Cells - pathology Gastrointestinal diseases Gene expression Genes Genetic testing Genetic transcription Genome-Wide Association Study - methods Genomes Genomics Genotype & phenotype Humans Ileum Ileum - pathology Ileum - surgery Infant, Newborn Infants Infants (Premature) Intestine Intestines - pathology Laser Capture Microdissection - adverse effects Laser Capture Microdissection - methods Methylation Models, Animal Necrosis Necrotizing enterocolitis Neonates Pathogenesis Phenotypes Phenotyping Precision medicine Premature birth Ribonucleic acid RNA RNA sequencing Sequence Analysis, RNA - methods Sulfites Surgery Transcription Transcriptome - genetics Transcriptomics |
| title | Global hypermethylation of intestinal epithelial cells is a hallmark feature of neonatal surgical necrotizing enterocolitis |
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