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Series GSE81547 Query DataSets for GSE81547
Status Public on Sep 28, 2017
Title Single cell transcriptome analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns.
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary As organisms age, cells accumulate genetic and epigenetic changes that eventually lead to impaired organ function or catastrophic failure such as cancer. Here we describe a single-cell transcriptome analysis of 2544 human pancreas cells from donors, spanning six decades of life. We find that islet cells from older donors have increased levels of disorder as measured both by noise in the transcriptome and by the number of cells which display inappropriate hormone expression, revealing a transcriptional instability associated with aging. By analyzing the spectrum of somatic mutations in single cells from previously-healthy donors, we find a specific age-dependent mutational signature characterized by C to A and C to G transversions, indicators of oxidative stress, which is absent in single cells from human brain tissue or in a tumor cell line. Cells carrying a high load of such mutations also express higher levels of stress and senescence markers, including FOS, JUN, and the cytoplasmic superoxide dismutase SOD1, markers previously linked to pancreatic diseases with substantial age-dependent risk, such as type 2 diabetes mellitus and adenocarcinoma. Thus, our single-cell approach unveils gene expression changes and somatic mutations acquired in aging human tissue, and identifies molecular pathways induced by these genetic changes that could influence human disease. Also, our results demonstrate the feasibility of using single-cell RNA-seq data from primary cells to derive meaningful insights into the genetic processes that operate on aging human tissue and to determine which molecular mechanisms are coordinated with these processes.
 
Overall design Examination of single cells from primary human pancreas tissue
Web link https://www.biorxiv.org/content/early/2017/02/13/108043
 
Contributor(s) Enge M, Arda E
Citation(s) 28965763
Submission date May 18, 2016
Last update date Mar 14, 2019
Contact name Martin Enge
E-mail martin.enge@gmail.com
Organization name Stanford University
Department Bioengineering
Lab Stephen Quake
Street address James H. Clark Center, 318 Campus Drive,
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (2544)
GSM2171880 21yr_male_cell1
GSM2171881 21yr_male_cell2
GSM2171882 21yr_male_cell3
Relations
BioProject PRJNA322355
SRA SRP075496

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Supplementary file Size Download File type/resource
GSE81547_RAW.tar 168.3 Mb (http)(custom) TAR (of CSV)
Processed data provided as supplementary file
Raw data are available in SRA

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