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Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates
Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927156/ https://www.ncbi.nlm.nih.gov/pubmed/33378680 http://dx.doi.org/10.1016/j.celrep.2020.108562 |
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author | Patananan, Alexander N. Sercel, Alexander J. Wu, Ting-Hsiang Ahsan, Fasih M. Torres, Alejandro Kennedy, Stephanie A.L. Vandiver, Amy Collier, Amanda J. Mehrabi, Artin Van Lew, Jon Zakin, Lise Rodriguez, Noe Sixto, Marcos Tadros, Wael Lazar, Adam Sieling, Peter A. Nguyen, Thang L. Dawson, Emma R. Braas, Daniel Golovato, Justin Cisneros, Luis Vaske, Charles Plath, Kathrin Rabizadeh, Shahrooz Niazi, Kayvan R. Chiou, Pei-Yu Teitell, Michael A. |
author_facet | Patananan, Alexander N. Sercel, Alexander J. Wu, Ting-Hsiang Ahsan, Fasih M. Torres, Alejandro Kennedy, Stephanie A.L. Vandiver, Amy Collier, Amanda J. Mehrabi, Artin Van Lew, Jon Zakin, Lise Rodriguez, Noe Sixto, Marcos Tadros, Wael Lazar, Adam Sieling, Peter A. Nguyen, Thang L. Dawson, Emma R. Braas, Daniel Golovato, Justin Cisneros, Luis Vaske, Charles Plath, Kathrin Rabizadeh, Shahrooz Niazi, Kayvan R. Chiou, Pei-Yu Teitell, Michael A. |
author_sort | Patananan, Alexander N. |
collection | PubMed |
description | Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (ρ0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration. However, SIMR fibroblasts maintain a ρ0-like cell metabolome and transcriptome despite growth in restrictive media. We reprogrammed non-immortal SIMR fibroblasts into induced pluripotent stem cells (iPSCs) with subsequent differentiation into diverse functional cell types, including mesenchymal stem cells (MSCs), adipocytes, osteoblasts, and chondrocytes. Remarkably, after reprogramming and differentiation, SIMR fibroblasts molecularly and phenotypically resemble unmanipulated control fibroblasts carried through the same protocol. Thus, our MitoPunch “pipeline” enables the production of SIMR cells with unique mtDNA-nDNA combinations for additional studies and applications in multiple cell types. |
format | Online Article Text |
id | pubmed-7927156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-79271562021-03-03 Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates Patananan, Alexander N. Sercel, Alexander J. Wu, Ting-Hsiang Ahsan, Fasih M. Torres, Alejandro Kennedy, Stephanie A.L. Vandiver, Amy Collier, Amanda J. Mehrabi, Artin Van Lew, Jon Zakin, Lise Rodriguez, Noe Sixto, Marcos Tadros, Wael Lazar, Adam Sieling, Peter A. Nguyen, Thang L. Dawson, Emma R. Braas, Daniel Golovato, Justin Cisneros, Luis Vaske, Charles Plath, Kathrin Rabizadeh, Shahrooz Niazi, Kayvan R. Chiou, Pei-Yu Teitell, Michael A. Cell Rep Article Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (ρ0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration. However, SIMR fibroblasts maintain a ρ0-like cell metabolome and transcriptome despite growth in restrictive media. We reprogrammed non-immortal SIMR fibroblasts into induced pluripotent stem cells (iPSCs) with subsequent differentiation into diverse functional cell types, including mesenchymal stem cells (MSCs), adipocytes, osteoblasts, and chondrocytes. Remarkably, after reprogramming and differentiation, SIMR fibroblasts molecularly and phenotypically resemble unmanipulated control fibroblasts carried through the same protocol. Thus, our MitoPunch “pipeline” enables the production of SIMR cells with unique mtDNA-nDNA combinations for additional studies and applications in multiple cell types. 2020-12-29 /pmc/articles/PMC7927156/ /pubmed/33378680 http://dx.doi.org/10.1016/j.celrep.2020.108562 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Patananan, Alexander N. Sercel, Alexander J. Wu, Ting-Hsiang Ahsan, Fasih M. Torres, Alejandro Kennedy, Stephanie A.L. Vandiver, Amy Collier, Amanda J. Mehrabi, Artin Van Lew, Jon Zakin, Lise Rodriguez, Noe Sixto, Marcos Tadros, Wael Lazar, Adam Sieling, Peter A. Nguyen, Thang L. Dawson, Emma R. Braas, Daniel Golovato, Justin Cisneros, Luis Vaske, Charles Plath, Kathrin Rabizadeh, Shahrooz Niazi, Kayvan R. Chiou, Pei-Yu Teitell, Michael A. Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates |
title | Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates |
title_full | Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates |
title_fullStr | Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates |
title_full_unstemmed | Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates |
title_short | Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates |
title_sort | pressure-driven mitochondrial transfer pipeline generates mammalian cells of desired genetic combinations and fates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927156/ https://www.ncbi.nlm.nih.gov/pubmed/33378680 http://dx.doi.org/10.1016/j.celrep.2020.108562 |
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