TY - JOUR
T1 - Horizontal mtDNA transfer between cells is common during mouse development
AU - Marti Gutierrez, Nuria
AU - Mikhalchenko, Aleksei
AU - Ma, Hong
AU - Koski, Amy
AU - Li, Ying
AU - Van Dyken, Crystal
AU - Tippner-Hedges, Rebecca
AU - Yoon, David
AU - Liang, Dan
AU - Hayama, Tomonari
AU - Battaglia, David
AU - Kang, Eunju
AU - Lee, Yeonmi
AU - Barnes, Anthony Paul
AU - Amato, Paula
AU - Mitalipov, Shoukhrat
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/3/18
Y1 - 2022/3/18
N2 - 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.
AB - 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.
KW - Cell biology
KW - Developmental biology
KW - Molecular biology
UR - http://www.scopus.com/inward/record.url?scp=85124994500&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124994500&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.103901
DO - 10.1016/j.isci.2022.103901
M3 - Article
AN - SCOPUS:85124994500
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 3
M1 - 103901
ER -