Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis.
Selective hypermethylation is evident in small intestine samples from infants with necrotizing enterocolitis.
复制标题
选择性高甲基化在来自坏死小肠结肠炎的婴儿的小肠样本中很明显。
DOI：
10.1186/s13148-022-01266-y
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发表时间：
2022-04-11
影响因子：
5.7
通讯作者：
Peters D
中科院分区：
文献类型：
--
作者：
Good M;Chu T;Shaw P;Nolan LS;Wrobleski J;Castro C;Gong Q;DeWitt O;Finegold DN;Peters D
坏死性小肠结肠炎（NEC）是最常见的胃肠道疾病，影响了NEC，其特征是肠道屏障破坏，炎症反应，肠子坏死和多型系统器官的疾病。
为了进一步了解支持NEC的分子机制，我们使用了溶液相杂交和黑素转化DNA的下一代DNA测序，以对高读取深度的DNA甲基化进行针对性的全基因组分析。
我们发现，相对于非NEC的甲基化状态，来自手术NEC婴儿的回肠样品（n = 5）存在于其非NEC的同行（n = 9）。我们还发现，在回肠NEC组织中鉴定出的DNA甲基化模式与先前在受NEC影响的婴儿的粪便样品中发现并发表的DNA甲基化模式相关。
We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. This, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These调查结果将来的研究将涉及在NEC发作之前获得的样品的纵向筛选。
在线版本包含的补充材料可获得10.1186/s13148-022-01266-y。
Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear. To further understand the molecular mechanisms that support NEC, we used solution phase hybridization and next-generation DNA sequencing of bisulfite converted DNA to perform targeted genome-wide analysis of DNA methylation at high read depth. We found that ileal samples from surgical NEC infants (n = 5) exist in a broadly hypermethylated state relative to their non-NEC counterparts (n = 9). These trends were not uniform, with hypermethylation being most consistently observed outside CpG islands and promoters. We further identified several biologically interesting gene promoters that displayed differential methylation in NEC and a number of biological pathways that appear dysregulated in NEC. We also found that DNA methylation patterns identified in ileal NEC tissue were correlated with those found and published previously in stool samples from NEC-affected infants. We confirmed that surgical NEC is associated with broad DNA hypermethylation in the ileum, and this may be detectable in stool samples of affected individuals. Thus, an epigenomic liquid biopsy of stool may have significant potential as a biomarker with respect to the diagnostic/predictive detection of NEC. Our findings, along with recent similar observations in colon, suggest that epigenomic dysregulation is a significant feature of surgical NEC. These findings motivate future studies which will involve the longitudinal screening of samples obtained prior to the onset of NEC. Our long-term goal is the development of novel screening, diagnostic and phenotyping methods for NEC. The online version contains supplementary material available at 10.1186/s13148-022-01266-y.
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影响因子：
5.9
作者：
Klooster JPT;Bol-Schoenmakers M;van Summeren K;van Vliet ALW;de Haan CAM;van Kuppeveld FJM;Verkoeijen S;Pieters R
通讯作者：
Pieters R
影响因子：
3.6
作者：
Walsh, Michele C.;Bell, Edward F.;Truog, William E.
通讯作者：
Truog, William E.
DOI：
10.1016/j.xcrm.2021.100320
发表时间：
2021-06-15
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Mihi B;Gong Q;Nolan LS;Gale SE;Goree M;Hu E;Lanik WE;Rimer JM;Liu V;Parks OB;Lewis AN;Agrawal P;Laury ML;Kumar P;Huang E;Bidani SS;Luke CJ;Kolls JK;Good M
通讯作者：
Good M
影响因子：
5.3
作者：
Lee, Sei-Jung;Leoni, Giovanna;Yun, C. Chris
通讯作者：
Yun, C. Chris
影响因子：
8
作者：
Bisquera, JA;Cooper, TR;Berseth, CL
通讯作者：
Berseth, CL