دورية أكاديمية

Integrative genome-scale analyses reveal post-transcriptional signatures of early human small intestinal development in a directed differentiation organoid model.

التفاصيل البيبلوغرافية
العنوان: Integrative genome-scale analyses reveal post-transcriptional signatures of early human small intestinal development in a directed differentiation organoid model.
المؤلفون: Hung YH; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Capeling M; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Villanueva JW; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Kanke M; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Shanahan MT; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Huang S; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA., Cubitt R; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Rinaldi VD; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Schimenti JC; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Spence JR; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA., Sethupathy P; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. pr46@cornell.edu.
المصدر: BMC genomics [BMC Genomics] 2023 Oct 26; Vol. 24 (1), pp. 641. Date of Electronic Publication: 2023 Oct 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 100965258 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2164 (Electronic) Linking ISSN: 14712164 NLM ISO Abbreviation: BMC Genomics Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2000-
مواضيع طبية MeSH: Gene Expression Regulation, Developmental* , MicroRNAs*/genetics , MicroRNAs*/metabolism, Humans ; Animals ; Mice ; Cell Differentiation/genetics ; Intestine, Small/metabolism ; Organoids/metabolism
مستخلص: Background: MicroRNAs (miRNAs) are important post-transcriptional gene regulators controlling cellular lineage specification and differentiation during embryonic development, including the gastrointestinal system. However, miRNA-mediated regulatory mechanisms involved in early embryonic development of human small intestine (SI) remains underexplored. To explore candidate roles for miRNAs in prenatal SI lineage specification in humans, we used a multi-omic analysis strategy in a directed differentiation model that programs human pluripotent stem cells toward the SI lineage.
Results: We leveraged small RNA-seq to define the changing miRNA landscape, and integrated chromatin run-on sequencing (ChRO-seq) and RNA-seq to define genes subject to significant post-transcriptional regulation across the different stages of differentiation. Small RNA-seq profiling revealed temporal dynamics of miRNA signatures across different developmental events of the model, including definitive endoderm formation, SI lineage specification and SI regional patterning. Our multi-omic, integrative analyses showed further that the elevation of miR-182 and reduction of miR-375 are key events during SI lineage specification. We demonstrated that loss of miR-182 leads to an increase in the foregut master marker SOX2. We also used single-cell analyses in murine adult intestinal crypts to support a life-long role for miR-375 in the regulation of Zfp36l2. Finally, we uncovered opposing roles of SMAD4 and WNT signaling in regulating miR-375 expression during SI lineage specification. Beyond the mechanisms highlighted in this study, we also present a web-based application for exploration of post-transcriptional regulation and miRNA-mediated control in the context of early human SI development.
Conclusion: The present study uncovers a novel facet of miRNAs in regulating prenatal SI development. We leveraged multi-omic, systems biology approaches to discover candidate miRNA regulators associated with early SI developmental events in a human organoid model. In this study, we highlighted miRNA-mediated post-transcriptional regulation relevant to the event of SI lineage specification. The candidate miRNA regulators that we identified for the other stages of SI development also warrant detailed characterization in the future.
(© 2023. The Author(s).)
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معلومات مُعتمدة: P30 DK034933 United States DK NIDDK NIH HHS; R21 HD104922 United States HD NICHD NIH HHS; U01 DK103141 United States DK NIDDK NIH HHS; 5P30DK034933 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: Development; Functional genomics; Intestine; Micro-RNA; Post-transcriptional regulation
المشرفين على المادة: 0 (MicroRNAs)
تواريخ الأحداث: Date Created: 20231026 Date Completed: 20231030 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10601309
DOI: 10.1186/s12864-023-09743-1
PMID: 37884859
قاعدة البيانات: MEDLINE
الوصف
تدمد:1471-2164
DOI:10.1186/s12864-023-09743-1