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Transcriptional analysis of islets of Langerhans from organ donors of different ages

Seiron, Peter ; Stenwall, Anton ; Hedin, Anders ; Granlund, Louise ; Esguerra, Jonathan Lou S. LU orcid ; Volkov, Petr LU ; Renström, Erik LU ; Korsgren, Olle ; Lundberg, Marcus and Skog, Oskar (2021) In PLoS ONE 16(3 March).
Abstract

Insulin secretion is impaired with increasing age. In this study, we aimed to determine whether aging induces specific transcriptional changes in human islets. Laser capture microdissection was used to extract pancreatic islet tissue from 37 deceased organ donors aged 1–81 years. The transcriptomes of the extracted islets were analysed using Ion AmpliSeq sequencing. 346 genes that co-vary significantly with age were found. There was an increased transcription of genes linked to senescence, and several aspects of the cell cycle machinery were downregulated with increasing age. We detected numerous genes not linked to aging in previous studies likely because earlier studies analysed islet cells isolated by enzymatic digestion which might... (More)

Insulin secretion is impaired with increasing age. In this study, we aimed to determine whether aging induces specific transcriptional changes in human islets. Laser capture microdissection was used to extract pancreatic islet tissue from 37 deceased organ donors aged 1–81 years. The transcriptomes of the extracted islets were analysed using Ion AmpliSeq sequencing. 346 genes that co-vary significantly with age were found. There was an increased transcription of genes linked to senescence, and several aspects of the cell cycle machinery were downregulated with increasing age. We detected numerous genes not linked to aging in previous studies likely because earlier studies analysed islet cells isolated by enzymatic digestion which might affect the islet transcriptome. Among the novel genes demonstrated to correlate with age, we found an upregulation of SPP1 encoding osteopontin. In beta cells, osteopontin has been seen to be protective against both cytotoxicity and hyperglycaemia. In summary, we present a transcriptional profile of aging in human islets and identify genes that could affect disease course in diabetes.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
16
issue
3 March
article number
e0247888
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:33711030
  • scopus:85102656205
ISSN
1932-6203
DOI
10.1371/journal.pone.0247888
language
English
LU publication?
yes
id
bc840aca-e5b2-4bb0-8f0f-7e2fb26e22a7
date added to LUP
2021-03-24 13:23:44
date last changed
2024-05-02 05:17:54
@article{bc840aca-e5b2-4bb0-8f0f-7e2fb26e22a7,
  abstract     = {{<p>Insulin secretion is impaired with increasing age. In this study, we aimed to determine whether aging induces specific transcriptional changes in human islets. Laser capture microdissection was used to extract pancreatic islet tissue from 37 deceased organ donors aged 1–81 years. The transcriptomes of the extracted islets were analysed using Ion AmpliSeq sequencing. 346 genes that co-vary significantly with age were found. There was an increased transcription of genes linked to senescence, and several aspects of the cell cycle machinery were downregulated with increasing age. We detected numerous genes not linked to aging in previous studies likely because earlier studies analysed islet cells isolated by enzymatic digestion which might affect the islet transcriptome. Among the novel genes demonstrated to correlate with age, we found an upregulation of SPP1 encoding osteopontin. In beta cells, osteopontin has been seen to be protective against both cytotoxicity and hyperglycaemia. In summary, we present a transcriptional profile of aging in human islets and identify genes that could affect disease course in diabetes.</p>}},
  author       = {{Seiron, Peter and Stenwall, Anton and Hedin, Anders and Granlund, Louise and Esguerra, Jonathan Lou S. and Volkov, Petr and Renström, Erik and Korsgren, Olle and Lundberg, Marcus and Skog, Oskar}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{3 March}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Transcriptional analysis of islets of Langerhans from organ donors of different ages}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0247888}},
  doi          = {{10.1371/journal.pone.0247888}},
  volume       = {{16}},
  year         = {{2021}},
}