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| Status |
Public on Mar 18, 2021 |
| Title |
Age-related changes in Pc gene regulation disrupt lineage fidelity in intestinal stem cells |
| Organism |
Drosophila melanogaster |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Tissue homeostasis requires long-term lineage fidelity of somatic stem cells. Whether and how age-related changes in somatic stem cells impact the faithful execution of lineage decisions remains largely unknown. Here, we address this question using genome-wide chromatin accessibility and transcriptome analysis as well as single cell RNA-seq to explore stem cell-intrinsic changes in the aging Drosophila intestine. These studies indicate that in stem cells of old flies, promoters of Polycomb (Pc) target genes become differentially accessible, resulting in the increased expression of enteroendocrine (EE) cell specification genes. Consistently, we find age-related changes in the composition of the EE progenitor cell population in aging intestines, as well as a significant increase in the proportion of EE-specified ISCs and progenitors in aging flies. We further confirm that Pc-mediated chromatin regulation is a critical determinant of EE cell specification in the Drosophila intestine. Pc is required to maintain expression of stem cell genes while ensuring repression of differentiation and specification genes. Our results identify Pc group proteins as central regulators of lineage identity in the intestinal epithelium and highlight the impact of age-related decline in chromatin regulation on tissue homeostasis.
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| Overall design |
We used ATAC-seq to compare the chromatin accessibility profiles of sorted intestinal stem cells from young, middle-aged and old Drosophila adults.
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| Contributor(s) |
Tauc H, Ronnen-Oron T |
| Citation(s) |
33724181 |
| |
| Submission date |
Jan 05, 2021 |
| Last update date |
Mar 18, 2021 |
| Contact name |
Tal Ronnen Oron |
| E-mail(s) |
talronor@gmail.com
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| Organization name |
Buck Institute for Research on Aging
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| Department |
Bioinformatics Core
|
| Street address |
8001 Redwood blvd.
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| City |
Novato |
| State/province |
CA |
| ZIP/Postal code |
94945 |
| Country |
USA |
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| Platforms (1) |
| GPL17275 |
Illumina HiSeq 2500 (Drosophila melanogaster) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA689843 |
| SRA |
SRP300536 |
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