Horizontal mtDNA transfer between cells is common during mouse development
Nuria Marti Gutierrez,
Aleksei Mikhalchenko,
Hong Ma,
Amy Koski,
Ying Li,
Crystal Van Dyken,
Rebecca Tippner-Hedges,
David Yoon,
Dan Liang,
Tomonari Hayama,
David Battaglia,
Eunju Kang,
Yeonmi Lee,
Anthony Paul Barnes,
Paula Amato,
Shoukhrat Mitalipov
Affiliations
Nuria Marti Gutierrez
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Aleksei Mikhalchenko
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Hong Ma
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Amy Koski
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Ying Li
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Crystal Van Dyken
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Rebecca Tippner-Hedges
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
David Yoon
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Dan Liang
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Tomonari Hayama
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
David Battaglia
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA
Eunju Kang
Stem Cell Center & Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
Yeonmi Lee
Stem Cell Center & Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
Anthony Paul Barnes
Knight Cardiovascular Institute, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA
Paula Amato
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA
Shoukhrat Mitalipov
Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, Portland, OR 97239, USA; Corresponding author
Summary: Cells transmit their genomes vertically to daughter cells during cell divisions. Here, we demonstrate the occurrence and extent of horizontal mitochondrial (mt)DNA acquisition between cells that are not in a parent-offspring relationship. Extensive single-cell sequencing from various tissues and organs of adult chimeric mice composed of cells carrying distinct mtDNA haplotypes showed that a substantial fraction of individual cardiomyocytes, neurons, glia, intestinal, and spleen cells captured donor mtDNA at high levels. In addition, chimeras composed of cells with wild-type and mutant mtDNA exhibited increased trafficking of wild-type mtDNA to mutant cells, suggesting that horizontal mtDNA transfer may be a compensatory mechanism to restore compromised mitochondrial function. These findings establish the groundwork for further investigations to identify mtDNA donor cells and mechanisms of transfer that could be critical to the development of novel gene therapies.
