Cited by 582Single-cell and spatial transcriptomicsPancreatic function and diabetesGenetics, Aging, and Longevity in Model Organisms

Single-Cell Analysis of Human Pancreas Reveals Transcriptional Signatures of Aging and Somatic Mutation Patterns

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Enge, Martin, Arda, H. Efsun, Mignardi, Marco, Beausang, John, Bottino, Rita, Kim, Seung K., Quake, Stephen R.·2017·Cell

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Abstract

As organisms age, cells accumulate genetic and epigenetic errors that eventually lead to impaired organ function or catastrophic transformation such as cancer. Because aging reflects a stochastic process of increasing disorder, cells in an organ will be individually affected in different ways, thus rendering bulk analyses of postmitotic adult cells difficult to interpret. Here, we directly measure the effects of aging in human tissue by performing single-cell transcriptome analysis of 2,544 human pancreas cells from eight donors spanning six decades of life. We find that islet endocrine cells from older donors display increased levels of transcriptional noise and potential fate drift. By determining the mutational history of individual cells, we uncover a novel mutational signature in healthy aging endocrine cells. Our results demonstrate the feasibility of using single-cell RNA sequencing (RNA-seq) data from primary cells to derive insights into genetic and transcriptional processes that operate on aging human tissue.

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Crossref · 10.1016/j.cell.2017.09.004

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  • Alternative measures of cell-cell heterogeneity using heuristically selected subsets of genes were highly correlated with the primary method.

    “We also considered alternative measures of cell–cell heterogeneity using heuristically selected subsets of genes as in previous reports (Enge et al. 2017; Angelidis et al. 2019) and found that results were highly correlated with our primary method (Supplemental Fig. S12; Supplemental Methods).”
  • Two data sets of the human cell atlas were used: a Drop-seq data set measured in lung tissue52 and a Smart-seq2 data set measured in pancreas tissue51.

    “Two data sets of the human cell atlas were used for that, a Drop-seq data set measured in lung tissue52 and a Smart-seq2 data set measured in pancreas tissue51.”
  • Single cell RNA sequencing studies show greater cell-to-cell variability in gene expression in human T cells and pancreatic cells, as well as differences in cellular mutation rates with age.

    “These observations are supported by a rapidly growing number of single cell RNA sequencing studies showing greater cell-to-cell variability in gene expression in human T cells and pancreatic cells, as well as differences in cellular mutation rates with age.47,48”

    From Asynchronous, contagious and digital aging (2021) · cites this paper as [48]

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Authors
Enge, M., Arda, H. E., Mignardi, M., Beausang, J., Bottino, R., Kim, S. K., & Quake, S. R.
Affiliations
  • Stanford University (US)
  • Stanford Medicine (US)
  • Uppsala University (SE)
  • Allegheny Health Network (US)
Corresponding author
Quake, Stephen R.
Venue
Cell
Publisher
Elsevier BV
Published
2017-10
Volume
171
Issue
2
Pages
321-330.e14
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2758815122
Cited by
568
References
56
Citations by year
2026: 40 · 2025: 51 · 2024: 69 · 2023: 78 · 2022: 77 · 2021: 82 · 2020: 79 · 2019: 46 · 2018: 42 · 2017: 3 · 2015: 1
FWCI
18.98
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • California Institute for Regenerative Medicine (GC1R-06673)
  • Center of Excellence for Stem Cell Genomics and NIH (U01-HL099999, U01-HL099995)
  • NIH (UC4DK104211, DK10261201, P30DK116074-01)
  • Helmsley Charitable Trust
  • H.L. Snyder Foundation
  • Elser Foundation
  • JDRF (3-APF-2016-172-A-N)
  • Wallenberg Research link at Stanford University (2013.0391)
  • NIDDK (5T32DK007217-39)
  • Swedish Research Council (2015-00599)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
human aging, pancreatic islets, endocrine cells, somatic mutations, mutational signatures, transcriptional noise, single-cell transcriptomics, tissue aging, cellular heterogeneity
MeSH terms
Adult, Aging, Child, Child, Preschool, Humans, Infant, Middle Aged, Mutation, Pancreas, Transcription, Genetic, Cellular Senescence, Sequence Analysis, RNA, Polymorphism, Single Nucleotide, Single-Cell Analysis

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