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Series GSE173806 Query DataSets for GSE173806
Status Public on Jun 27, 2022
Title Cellular and extracellular tRNA-derived fragments demonstrate distinct signatures in cellular stress
Organisms Homo sapiens; Rattus norvegicus
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may yield novel biomarkers for different diseases, and potentially identify key signaling pathways important for disease progression . tRNA and tRNA-derived small RNAs (tDRs) comprise one of the most abundant RNA species in cells and have been associated with cellular stress responses. However, systematic characterization of tDRs have been challenged by the technical difficulties in accurately profiling tDRs with normal small RNA sequencing techniques due to the presence of RNA modifications. Here we use AlkB-facilitated methylation sequencing (ARM-seq) to uncover a comprehensive landscape of cellular and extracellular tDRs expression in a variety of human and rat cells during common stress responses, including nutrition deprivation, hypoxia, and oxidative stress. We found that extracellular tDRs have a distinct fragmentation signature with a predominant length of 31-33 nts and a highly specific termination position when compared with intracellular tDRs, and comprise signatures that improve discrimination of different cellular stress responses compared to extracellular miRNAs. Distinct extracellular tDR signatures for each profiled stressor are elucidated in 4 different types of cells. This distinct extracellular tDR fragmentation pattern is also noted in plasma extracellular RNA from patients on cardiopulmonary bypass with significant overlap with the signatures of nutrition depravation and oxidative stress in our cellular models, providing preliminary in vivo correlation of our findings. Future application of our findings to human disease models may have promise in yielding novel biomarkers.
 
Overall design Cellular and extracellular tDRs expression profiles of 4 cell types under 4 different treatments (3 independent replicates for each condition)
 
Contributor(s) Li G, Manning A, Bagi A, Yang X, Howard J, Chan P, Sweeney T, Laurent B, Li H, Kontaridis M, Laurent LC, Van Keuren-Jensen K, Muehlschlegel JD, Kitchen R, Lowe TM, Das S
Citation(s) 35373532
Submission date May 04, 2021
Last update date Jun 27, 2022
Contact name Guoping Li
E-mail(s) gli21@mgh.harvard.edu
Organization name Massachusetts General Hospital
Department CVRC
Lab Dr. Saumya Das
Street address Cardiovascular Research Center, 185 Cambridge St, Simches 3.5000
City Boston
State/province MA
ZIP/Postal code 02114
Country USA
 
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18694 Illumina HiSeq 2500 (Rattus norvegicus)
Samples (96)
GSM5278846 CF_Ctrl_1
GSM5278847 CF_Ctrl_2
GSM5278848 CF_Ctrl_3
Relations
BioProject PRJNA727096
SRA SRP318389

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE173806_Human_normalized_readcounts.csv.gz 433.4 Kb (ftp)(http) CSV
GSE173806_Rat_normalized_readcounts.csv.gz 426.1 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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