التفاصيل البيبلوغرافية
| العنوان: |
Xenotransplanted human organoids identify transepithelial zinc transport as a key mediator of intestinal adaptation |
| المؤلفون: |
Maame Efua S. Sampah, Hannah Moore, Raheel Ahmad, Johannes Duess, Peng Lu, Carla Lopez, Steve Steinway, Daniel Scheese, Zachariah Raouf, Koichi Tsuboi, Jeffrey Ding, Connor Caputo, Madison McFarland, William B. Fulton, Sanxia Wang, Meghan Wang, Thomas Prindle, Vered Gazit, Deborah C. Rubin, Samuel Alaish, Chhinder P. Sodhi, David J. Hackam |
| المصدر: |
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024) |
| بيانات النشر: |
Nature Portfolio, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Science |
| مصطلحات موضوعية: |
Science |
| الوصف: |
Abstract Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, we identify the upregulation of SLC39A5 and associated transcription factor KLF5 in biopsied intestinal tissue specimens from patients with SBS. Thus, we identify zinc supplementation as a potential therapy for SBS and describe a xenotransplantation model that provides a platform for discovery in other intestinal diseases. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-52216-6 |
| URL الوصول: |
https://doaj.org/article/dd561572beec437e9141bc2d050317a4 |
| رقم الانضمام: |
edsdoj.561572beec437e9141bc2d050317a4 |
| قاعدة البيانات: |
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