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编目出生后第一个月内的产后小肠转录组。

Cataloguing the postnatal small intestinal transcriptome during the first postnatal month.

作者信息

Oliveira Luiz Fernando Silva, Khetani Radhika S, Wu Yu-Syuan, Dasuri Venkata Siva, Harrington Amanda W, Olaloye Oluwabunmi, Goldsmith Jeffrey, Breault David T, Konnikova Liza, Ho Sui Shannan J, O'Connell Amy E

机构信息

Division of Newborn Medicine, Boston Children's Hospital, Boston, MA.

Dept of Biostatistics, Harvard T.H. Chan School of Public Health.

出版信息

bioRxiv. 2024 Dec 27:2024.09.25.612672. doi: 10.1101/2024.09.25.612672.

Abstract

In the first postnatal month, the developing mouse intestine shifts from an immature to a mature intestine that will sustain the organism throughout the lifespan. Here, we surveyed the mouse intestine in C57Bl/6 mice by RNA-Seq to evaluate the changes in gene expression over time from the day of birth through 1 month of age in both the duodenum and ileum. We analyzed gene expression for changes in gene families that correlated with the periods of NEC susceptibility or resistance. We highlight that increased expression of DNA processing genes and vacuolar structure genes, tissue development and morphogenesis genes, and cell migration genes all correlated with NEC susceptibility, while increases in immunity gene sets, intracellular transport genes, ATP production, and intracellular metabolism genes correlated with NEC resistance. Using trends identified in the RNA-Seq analyses, we further evaluated expression of cellular markers and epithelial regulators, immune cell markers, and adenosine metabolism components. We confirmed key changes with qRT-PCR and immunofluorescence. In addition, we compared some findings to humans using human intestinal biopsies and organoids. This dataset can serve as a reference for other groups considering the role of single molecules or molecular families in early intestinal and postnatal development.

摘要

在出生后的第一个月,发育中的小鼠肠道从不成熟的肠道转变为成熟的肠道,这种成熟肠道将在整个生命周期中维持机体运转。在此,我们通过RNA测序对C57Bl/6小鼠的肠道进行了研究,以评估从出生日到1月龄期间十二指肠和回肠中基因表达随时间的变化。我们分析了与坏死性小肠结肠炎(NEC)易感性或抗性时期相关的基因家族的基因表达变化。我们强调,DNA处理基因、液泡结构基因、组织发育和形态发生基因以及细胞迁移基因的表达增加均与NEC易感性相关,而免疫基因集、细胞内运输基因、ATP生成以及细胞内代谢基因的增加与NEC抗性相关。利用RNA测序分析中确定的趋势,我们进一步评估了细胞标志物和上皮调节因子、免疫细胞标志物以及腺苷代谢成分的表达。我们通过定量逆转录聚合酶链反应(qRT-PCR)和免疫荧光证实了关键变化。此外,我们使用人类肠道活检组织和类器官将一些研究结果与人类进行了比较。该数据集可为其他考虑单个分子或分子家族在早期肠道和出生后发育中作用的研究团队提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a2d/11687594/a19bc43c4f4d/nihpp-2024.09.25.612672v2-f0001.jpg

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