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| Status |
Public on Nov 01, 2022 |
| Title |
Age-dependent Lamin remodeling induces cardiac dysfunction via dysregulation of cardiac transcriptional programs [RNA-Seq] |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
As we age, structural changes contribute to progressive decline in organ function, which in the heart acts through poorly characterized mechanisms. Utilizing the rapidly aging fruit fly model with its significant homology to the human cardiac proteome, we found that cardiomyocytes exhibit progressive loss of Lamin C (mammalian Lamin A/C homologue) with age. Unlike other tissues and laminopathies, we observe decreasing nuclear size, while nuclear stiffness increases. Premature genetic reduction of Lamin C phenocopies aging’s effects on the nucleus, and subsequently decreases heart contractility and sarcomere organization. Surprisingly, Lamin C reduction downregulates myogenic transcription factors and cytoskeletal regulators, possibly via reduced chromatin accessibility. Subsequently, we find an adult-specific role for cardiac transcription factors and show that maintenance of Lamin C sustains their expression and prevents age-dependent cardiac decline. Our findings are conserved in aged non-human primates and mice, demonstrating age-dependent nuclear remodeling is a major mechanism contributing to cardiac dysfunction.
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| Overall design |
Bulk RNA-Sequencing of Drosophila melanogaster isolated hearts, conducted for two control fly strains at 1 week of age (w1118, n = 4; attp2, n = 5) and 5 weeks of age (w1118, n = 4; attp2, n = 5) , and flies expressing Lamin C RNAi from the heart specific, Hand promoter at 1 week of age (n = 5). The purpose of sequencing was, 1) To Identify differentially expressed genes upon aging that may contribute to age-dependent nuclear remodeling in w1118 flies; 2) Show conserved age-dependent changes in gene expression across wildtype control strains (w1118 and attp2); and 3) Identify overlapping co-regulated genes upon aging (attp2 1- and 5-week aged flies) and Lamin C RNAi expressing flies.
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| Contributor(s) |
Engler AJ, Kirkland NJ |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Oct 15, 2021 |
| Last update date |
Nov 01, 2022 |
| Contact name |
Adam Jeffrey Engler |
| E-mail(s) |
aengler@ucsd.edu
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| Phone |
858-246-0678
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| Organization name |
UC San Diego
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| Department |
Bioengineering
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| Street address |
9500 Gilman Drive, MC 0412
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
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| Samples (23)
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| This SubSeries is part of SuperSeries: |
| GSE185968 |
Age-dependent Lamin remodeling induces cardiac dysfunction via dysregulation of cardiac transcriptional programs |
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| Relations |
| BioProject |
PRJNA771565 |
| SRA |
SRP341577 |
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