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| Status |
Public on Sep 20, 2022 |
| Title |
A BDNF-TrkB autocrine loop enhances senescent cell viability [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory and tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions selectively eliminate senescent cells. In this study, a drug library screen uncovered TrkB (NTRK2) inhibitors as selectively capable of triggering apoptosis of senescent, but not proliferating, human fibroblasts. Senescent cells expressed high levels of TrkB, which supported senescent cell viability, and secreted the TrkB ligand BDNF. The reduced viability of senescent cells after ablating BDNF function supported an autocrine function for TrkB and BDNF, and the increased expression of BCL2L2 through ERK5, downstream of BDNF-TrkB, favored senescent cell survival. Strikingly, treatment with TrkB inhibitors reduced the accumulation of senescent cells in aged mouse organs. Our results suggest that the SASP factor BDNF promotes cell survival by activating TrkB and is a promising therapeutic target to reduce the senescent cell burden.
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| Overall design |
We sequenced the mRNA present in WI-38 senescent cells in which either TrkB or BDNF were silenced (siNTRK2 and siBDNF, respectively) compared to siCtrl siRNA, and included siCtrl-transfected proliferating cells as well.
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| Contributor(s) |
Anerillas C, Herman AB, Munk R, Payea MJ, Rossi M, Tsitsipatis D, Martindale JL, Piao Y, Mazan-Mamczarz K, Fan J, Cui CY, De S, Abdelmohsen K, de Cabo R, Gorospe M |
| Citation(s) |
36266274 |
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| Submission date |
Dec 15, 2021 |
| Last update date |
Oct 28, 2022 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE202951 |
A BDNF-TrkB autocrine loop enhances senescent cell viability |
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| Relations |
| BioProject |
PRJNA789266 |
| SRA |
SRP351348 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE190998_RAW.tar |
2.4 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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