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Single cell transcriptome analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns.

Updated November 15, 2021

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. Examination of single cells from primary human pancreas tissue

Martin Enge1
1Stanford University
Laura Huerta
Matthew Green

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Analysis Portals

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UCSC Cell BrowserUCSC Cell Browser

Project Label

Single cell transcriptome analysis of human pancreas


Homo sapiens

Sample Type


Anatomical Entity


Organ Part

islet of Langerhans

Selected Cell Types


Disease Status (Specimen)


Disease Status (Donor)


Development Stage

4 development stages

Library Construction Method


Nucleic Acid Source

single cell

Paired End


Analysis Protocol

MultiSampleSmartSeq2_v2.2.6, SmartSeq2SingleSample_v5.1.5

File Format

6 file formats

Cell Count Estimate


Donor Count

bai2,544 file(s)bam2,544 file(s)csv1 file(s)fastq.gz5,088 file(s)loom1 file(s)tar1 file(s)