The Tkemaladze Method maps cell lineage with mutant mitochondrial transfer

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Published: 2025-09-30
DOI: https://doi.org/10.5281/zenodo.17236869
Keywords:
Cell Lineage Tracing, Mitochondrial DNA, Mitochondrial Transfer, Heteroplasmy, Developmental Biology, Progenitor Cells, Chimeric Model, Cytogenealogical Map, Regenerative Medicine

Main Article Content

Jaba Tkemaladze
Longevity Clinic
https://orcid.org/0000-0001-8651-7243

Abstract

The comprehensive mapping of cellular lineages from the zygote to a fully formed organism remains a fundamental and unresolved challenge in developmental biology. While modern single-cell technologies offer snapshots of cellular heterogeneity, they lack the inherent, permanent markers required to trace progeny through the complex events of asymmetric division and migration over time. This work introduces the Tkemaladze Method, a novel lineage-tracing approach that utilizes mutant mitochondrial DNA (mtDNA) as a stable, inheritable genetic label. The method involves the isolation of mitochondria from cytoplasts harboring known pathogenic mtDNA mutations and their microinjection into murine embryonic stem cells (mESCs). We confirmed successful transfer and functional integration via fluorescence microscopy and quantitative PCR. These labeled progenitor cells were used to generate chimeric embryos, where we demonstrated stable heteroplasmy and faithful inheritance of the mutant mtDNA in clonal progeny throughout development. Using fluorescent reporters, we visualized the fate of individual progenitors, enabling the quantitative construction of a detailed cytogenealogical map across tissues like the central nervous system, liver, and myocardium. A key finding was the tissue-specific segregation of mitochondrial tags, revealing selective pressure in high-energy-demand tissues. The Tkemaladze Method thus provides an unprecedented, powerful tool for fundamental developmental biology, disease modeling, and tracking the fate of transplanted cells in regenerative medicine.

Article Details

Issue

Vol. 1 No. 4 (2025)

Section

Research Article
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Articles published in Longevity Horizon fall under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). This means authors retain their copyright while granting the journal the right to be the first publisher. Readers are permitted to share and distribute the work as long as proper credit is given. However, the content may not be altered, modified, or used for commercial purposes.

Author Biography

Jaba Tkemaladze, Longevity Clinic

A physician-scientist specializing in the biology of ageing and longevity. His research focuses on the potential of stem cell therapies for age-related diseases and healthspan extension.

Current Roles:

  • President, Longevity Alliance Georgia.
  • Head of Department, Longevity Clinic, Inc., Georgia.

Research Focus:
His main research is related to the study of methodologies for returning the regeneration rate to the indicators of 12-24 years, in particular with the potential application of the technology of producing young safe stem cells from one's own somatic cells. His theoretical works include the development of the centriolar theory of differentiation and the centriolar theory of aging of the organism, which suggest the role of centrioles in the aging and development of cells and tissues.

Background:
Dr. Tkemaladze received his medical education at the Tbilisi State Medical University and continued his research in the laboratories of the Institute of Morphology and the Research Institute of Psychiatry. In his work, he uses a combined approach, combining experimental and computational methods, to study the aging process and develop treatments for age-related diseases.

Service and Recognition:
He has served on scientific advisory boards, including for the Georgian Ministry of Defense and the Longevity Alliance. He is the author of over 100 scientific publications and has been an invited speaker at numerous national and international conferences.

How to Cite

Tkemaladze, J. (2025). The Tkemaladze Method maps cell lineage with mutant mitochondrial transfer. Longevity Horizon, 1(4). DOI:https://doi.org/10.5281/zenodo.17236869
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