Cited by 224Pluripotent Stem Cells ResearchTelomeres, Telomerase, and SenescenceCRISPR and Genetic Engineering

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Influence of donor age on induced pluripotent stem cells

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Lo Sardo, Valentina, Ferguson, William, Erikson, Galina A, Topol, Eric J, Baldwin, Kristin K, Torkamani, Ali·2017·Nature Biotechnology

DOI 10.1038/nbt.3749PMC PMC5505172

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Abstract

Induced pluripotent stem cells (iPSCs) are being pursued as a source of cells for autologous therapies, many of which will be aimed at aged patients. To explore the impact of age on iPSC quality, we produced iPSCs from blood cells of 16 donors aged 21-100. We find that iPSCs from older donors retain an epigenetic signature of age, which can be reduced through passaging. Clonal expansion via reprogramming also enables the discovery of somatic mutations present in individual donor cells, which are missed by bulk sequencing methods. We show that exomic mutations in iPSCs increase linearly with age, and all iPSC lines analyzed carry at least one gene-disrupting mutation, several of which have been associated with cancer or dysfunction. Unexpectedly, elderly donors (>90 yrs) harbor fewer mutations than predicted, likely due to a contracted blood progenitor pool. These studies establish that donor age is associated with an increased risk of abnormalities in iPSCs and will inform clinical development of reprogramming technology.

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Authors: Lo Sardo, V., Ferguson, W., Erikson, G. A., Topol, E. J., Baldwin, K. K., & Torkamani, A.
Affiliations: Scripps Research Institute (US)
Corresponding author: Baldwin, Kristin K
Torkamani, Ali
ORCID: Ferguson, William
Erikson, Galina A
Topol, Eric J
Baldwin, Kristin K
Torkamani, Ali
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2016-12-12
Volume: 35
Issue: 1
Pages: 69-74
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/nbt.3749
PMC: PMC5505172
OpenAlex: W2566700840
Cited by: 223
References: 51
Citations by year: 2026: 18 · 2025: 15 · 2024: 22 · 2023: 19 · 2022: 20 · 2021: 23 · 2020: 25 · 2019: 25 · 2018: 35 · 2017: 20
FWCI: 13.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Biotechnology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (UL1TR001114, 8ul1tr000109-05)
National Institute on Aging (DP1AG055944)
National Heart, Lung, and Blood Institute (U01HL107436)
National Institute of Mental Health (R01MH102698)
National Human Genome Research Institute (U01HG006476)
National Institute of General Medical Sciences (U54GM114833)
National Center for Research Resources (UL1RR025774)
National Center for Advancing Translational Sciences (UL1-TR000109)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords: induced pluripotent stem cells, donor age, somatic mutations, clonal expansion, reprogramming, exome sequencing, autologous cell therapy, elderly patients
MeSH terms: Adult, Aged, Aging, Cell Differentiation, Cells, Cultured, Chromosome Aberrations, Female, Humans, Male, Middle Aged, Tissue Donors, Stem Cell Transplantation, Epigenesis, Genetic, Young Adult, Induced Pluripotent Stem Cells

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Influence of donor age on induced pluripotent stem cells

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