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De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans

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De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans. / Deuse, Tobias; Hu, Xiaomeng; Agbor-Enoh, Sean; Koch, Martina; Spitzer, Matthew H; Gravina, Alessia; Alawi, Malik; Marishta, Argit; Peters, Bjoern; Kosaloglu-Yalcin, Zeynep; Yang, Yanqin; Rajalingam, Raja; Wang, Dong; Nashan, Bjoern; Kiefmann, Rainer; Reichenspurner, Hermann; Valantine, Hannah; Weissman, Irving L; Schrepfer, Sonja.

In: NAT BIOTECHNOL, Vol. 37, No. 10, 10.2019, p. 1137-1144.

Research output: SCORING: Contribution to journal › Letter › Research › peer-review

Harvard

Deuse, T, Hu, X, Agbor-Enoh, S, Koch, M, Spitzer, MH, Gravina, A, Alawi, M, Marishta, A, Peters, B, Kosaloglu-Yalcin, Z, Yang, Y, Rajalingam, R, Wang, D, Nashan, B, Kiefmann, R, Reichenspurner, H, Valantine, H, Weissman, IL & Schrepfer, S 2019, 'De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans', NAT BIOTECHNOL, vol. 37, no. 10, pp. 1137-1144. https://doi.org/10.1038/s41587-019-0227-7

APA

Deuse, T., Hu, X., Agbor-Enoh, S., Koch, M., Spitzer, M. H., Gravina, A., Alawi, M., Marishta, A., Peters, B., Kosaloglu-Yalcin, Z., Yang, Y., Rajalingam, R., Wang, D., Nashan, B., Kiefmann, R., Reichenspurner, H., Valantine, H., Weissman, I. L., & Schrepfer, S. (2019). De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans. NAT BIOTECHNOL, 37(10), 1137-1144. https://doi.org/10.1038/s41587-019-0227-7

Vancouver

Deuse T, Hu X, Agbor-Enoh S, Koch M, Spitzer MH, Gravina A et al. De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans. NAT BIOTECHNOL. 2019 Oct;37(10):1137-1144. https://doi.org/10.1038/s41587-019-0227-7

Bibtex

@article{f4d738db9dd64d65907f8c1702d1f358,
title = "De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans",
abstract = "The utility of autologous induced pluripotent stem cell (iPSC) therapies for tissue regeneration depends on reliable production of immunologically silent functional iPSC derivatives. However, rejection of autologous iPSC-derived cells has been reported, although the mechanism underlying rejection is largely unknown. We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which has far less reliable repair mechanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and rejection. Here we present evidence in mice and humans that nonsynonymous mtDNA mutations can arise and become enriched during reprogramming to the iPSC stage, long-term culture and differentiation into target cells. These mtDNA mutations encode neoantigens that provoke an immune response that is highly specific and dependent on the host major histocompatibility complex genotype. Our results reveal that autologous iPSCs and their derivatives are not inherently immunologically inert for autologous transplantation and suggest that iPSC-derived products should be screened for mtDNA mutations.",
author = "Tobias Deuse and Xiaomeng Hu and Sean Agbor-Enoh and Martina Koch and Spitzer, {Matthew H} and Alessia Gravina and Malik Alawi and Argit Marishta and Bjoern Peters and Zeynep Kosaloglu-Yalcin and Yanqin Yang and Raja Rajalingam and Dong Wang and Bjoern Nashan and Rainer Kiefmann and Hermann Reichenspurner and Hannah Valantine and Weissman, {Irving L} and Sonja Schrepfer",
year = "2019",
month = oct,
doi = "10.1038/s41587-019-0227-7",
language = "English",
volume = "37",
pages = "1137--1144",
journal = "NAT BIOTECHNOL",
issn = "1087-0156",
publisher = "NATURE PUBLISHING GROUP",
number = "10",

}

RIS

TY - JOUR

T1 - De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans

AU - Deuse, Tobias

AU - Hu, Xiaomeng

AU - Agbor-Enoh, Sean

AU - Koch, Martina

AU - Spitzer, Matthew H

AU - Gravina, Alessia

AU - Alawi, Malik

AU - Marishta, Argit

AU - Peters, Bjoern

AU - Kosaloglu-Yalcin, Zeynep

AU - Yang, Yanqin

AU - Rajalingam, Raja

AU - Wang, Dong

AU - Nashan, Bjoern

AU - Kiefmann, Rainer

AU - Reichenspurner, Hermann

AU - Valantine, Hannah

AU - Weissman, Irving L

AU - Schrepfer, Sonja

PY - 2019/10

Y1 - 2019/10

N2 - The utility of autologous induced pluripotent stem cell (iPSC) therapies for tissue regeneration depends on reliable production of immunologically silent functional iPSC derivatives. However, rejection of autologous iPSC-derived cells has been reported, although the mechanism underlying rejection is largely unknown. We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which has far less reliable repair mechanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and rejection. Here we present evidence in mice and humans that nonsynonymous mtDNA mutations can arise and become enriched during reprogramming to the iPSC stage, long-term culture and differentiation into target cells. These mtDNA mutations encode neoantigens that provoke an immune response that is highly specific and dependent on the host major histocompatibility complex genotype. Our results reveal that autologous iPSCs and their derivatives are not inherently immunologically inert for autologous transplantation and suggest that iPSC-derived products should be screened for mtDNA mutations.

AB - The utility of autologous induced pluripotent stem cell (iPSC) therapies for tissue regeneration depends on reliable production of immunologically silent functional iPSC derivatives. However, rejection of autologous iPSC-derived cells has been reported, although the mechanism underlying rejection is largely unknown. We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which has far less reliable repair mechanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and rejection. Here we present evidence in mice and humans that nonsynonymous mtDNA mutations can arise and become enriched during reprogramming to the iPSC stage, long-term culture and differentiation into target cells. These mtDNA mutations encode neoantigens that provoke an immune response that is highly specific and dependent on the host major histocompatibility complex genotype. Our results reveal that autologous iPSCs and their derivatives are not inherently immunologically inert for autologous transplantation and suggest that iPSC-derived products should be screened for mtDNA mutations.

U2 - 10.1038/s41587-019-0227-7

DO - 10.1038/s41587-019-0227-7

M3 - Letter

C2 - 31427818

VL - 37

SP - 1137

EP - 1144

JO - NAT BIOTECHNOL

JF - NAT BIOTECHNOL

SN - 1087-0156

IS - 10

ER -