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 - Funding Information:
The authors acknowledge the OHSU Institutional Animal Care and Use Committee (IACUC) and Department of Comparative Medicine (DCM) for providing animal care, oversight, and guidance. We thank OHSU Vollum Institute, OHSU Flow Cytometry Core, and Molecular Technologies Core at ONPRC for their services and support. We are indebted to Hayley Darby, Riffat Ahmed, Thanasup Gonmanee, and Yibing Jia for their expertise and services. Studies were supported by the grants from the National Institutes of Health (NIH) (RO1AG062459), the Burroughs Wellcome Fund, the Collins Medical trust, National Research Foundation of Korea (NRF-2018R1A2B3001244), Asan Medical Center (2019-755), and OHSU institutional funds. N.M.G. A.M. P.A. and S.M. conceived the study and designed the experiments. C.V.D. managed mice colony. N.M.G. generated chimera embryos. D.L. T.H. C.V.D. and Y.L. performed embryo transfers. N.M.G. A.M. H.M. D.Y. D.L. T.H. and D.B. performed tissue collection, disaggregation into single cells, and single cells collection. N.M.G. A.M. D.Y. Y.L. C.V.D. R.T.H. A.K. D.L. and H.M. prepared samples for Sanger sequencing and performed qPCR. Y.L. E.K. and Y.Lee prepared mtDNA and performed MiSeq assays. N.M.G. A.M. and H.M performed NGS data analysis and interpretation. A.B. performed immunostaining. N.M.G. A.M. P.A. and S.M. analyzed data and wrote the paper. The authors declare no competing interest.
Funding Information:
The authors acknowledge the OHSU Institutional Animal Care and Use Committee (IACUC) and Department of Comparative Medicine (DCM) for providing animal care, oversight, and guidance. We thank OHSU Vollum Institute, OHSU Flow Cytometry Core, and Molecular Technologies Core at ONPRC for their services and support. We are indebted to Hayley Darby, Riffat Ahmed, Thanasup Gonmanee, and Yibing Jia for their expertise and services. Studies were supported by the grants from the National Institutes of Health (NIH) ( RO1AG062459 ), the Burroughs Wellcome Fund , the Collins Medical trust , National Research Foundation of Korea ( NRF-2018R1A2B3001244 ), Asan Medical Center ( 2019-755 ), and OHSU institutional funds.
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 -