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| Status |
Public on Aug 12, 2023 |
| Title |
Nutrient-driven dedifferentiation of enteroendocrine cells promotes adaptive intestinal growth |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Post-developmental organ resizing improves organismal fitness under constantly changing nutrient environments. Although stem cell abundance is a fundamental determinant of adaptive resizing, our understanding of its underlying mechanisms remains primarily limited to the regulation of stem cell division. Here, we demonstrate that nutrient fluctuation induces dedifferentiation in the Drosophila adult midgut to drive adaptive intestinal growth. From lineage tracing and single-cell RNA sequencing, we identify a subpopulation of enteroendocrine (EE) cells that convert into functional intestinal stem cells (ISCs) in response to dietary glucose and amino acids by activating the JAK-STAT pathway. Genetic ablation of EE-derived ISCs severely impairs ISC expansion and midgut growth despite the retention of resident ISCs, and in silico modeling further indicates that EE dedifferentiation enables an efficient increase in the midgut cell number while maintaining epithelial cell composition. Our findings identify a physiologically induced dedifferentiation that ensures ISC expansion during adaptive organ growth in concert with nutrient conditions.
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| Overall design |
Cells in the adult Drosophila midgut were collected from 1-day and 3-day old female adults and analysed by scRNA-seq.
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| Web link |
https://www.cell.com/developmental-cell/fulltext/S1534-5807(23)00437-9
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| Contributor(s) |
Nagai H, Nagai LA, Tasaki S, Nakato R, Miura M, Nakajima Y |
| Citation(s) |
37689060 |
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| Submission date |
Jul 07, 2022 |
| Last update date |
Nov 12, 2023 |
| Contact name |
Luis Augusto Eijy Nagai |
| E-mail(s) |
[email protected]
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| Organization name |
The University of Tokyo
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| Department |
Institute for Quantitative Biosciences
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| Lab |
Laboratory of Computational Genomics
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| Street address |
#201 Main building, Institute for Quantitative Biosciences, 1-1-1 Yayoi
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| City |
Bunkyo-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
113-0032 |
| Country |
Japan |
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| Platforms (1) |
| GPL32218 |
DNBSEQ-G400 (Drosophila melanogaster) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA856647 |
