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| Status |
Public on Sep 10, 2019 |
| Title |
PML2‐mediated thread‐like nuclear bodies mark late senescence in Hutchinson–Gilford progeria syndrome [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Regular nuclear structure is critical for genome maintenance and proper gene expression, disorder of which has a causal role in aging. Accumulation of Progerin in Hutchinson-Gilford progeria syndrome (HGPS) disrupts the integrity of nuclear lamina and causes nuclear structure abnormalities, leading to premature aging. However, the nuclear structure/function relationships in HGPS cells have not been well addressed, and roles of nuclear sub-compartments for HGPS pathogenesis are rarely reported. Here, evidence reveals that classical dot-like PML nuclear bodies (PML NBs) are reorganized into thread-like morphology in HGPS cells, and these irregular NBs are strongly associated with cell senescence. We demonstrate that farnesylated Progerin interacts with PML isoform 2 specifically, which accounts for the formation of thread-like PML NBs. Moreover, our findings uncover that irregular PML NBs perturb NBs-associated DNA repair and gene transcription, thereby promoting HGPS cell senescence. Thus, our work helps to clarify the roles of nuclear structure and sub-compartments such as PML NBs in cell aging, and evidence presented in this study strongly support that thread-like PML NBs could be a novel biomarker of human cell senescence.
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| Overall design |
Normal human dermal fibroblasts (NHDF) were transfected with control siRNA (NFcon) or pan-PML siRNA (NFsi) to analyze the expression of PML NBs-associated genes in NHDF cells. Fibroblasts from the Hutchinson-Gilford progeria syndrome (HGPS) patient were treated with control siRNA (HGcon), pan-PML siRNA (HGsi), PML2 siRNA (HGI2si), or FTI (2 uM of farnesylation inhibitor lonafarnib combined with 1 uM of zoledronate, HGFTI) for 3 days. High-throughput RNA sequencing were performed to analyze the differential gene expression between HGPS and NHDF, and to examine the 'rescue effect' of pan-PML siRNA, PML2 siRNA or FTI treatment on expression of PML NBs-associated genes in HGPS cells. Thus, there are total 6 groups of samples for RNA-seq, ie., NFcon, NFsi, HGcon, HGsi, HGI2si and HGFTI. Each group contains 3 replications, and siRNA sequence information was described in the supporting data of the manuscript.
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| Contributor(s) |
Wang M |
| Citation(s) |
32351002 |
| Submission date |
Sep 09, 2019 |
| Last update date |
Jun 17, 2020 |
| Contact name |
Baohua Liu |
| E-mail(s) |
ppliew@szu.edu.cn
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| Organization name |
Shenzhen University
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| Street address |
No.1066 Xueyuan Av. Nanshan District
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| City |
Shenzhen |
| ZIP/Postal code |
518060 |
| Country |
China |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE137085 |
PML2-mediated thread-like nuclear bodies mark late senescence in Hutchinson–Gilford progeria syndrome |
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| Relations |
| BioProject |
PRJNA564528 |
| SRA |
SRP221023 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE137083_RAW.tar |
49.9 Mb |
(http)(custom) |
TAR (of XLS) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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