Cell lineage inference from mitochondrial mutations

Hard, J.; Seidel, S.; Ferreira, P.; Berkes, P.; Jahn, K.; Eriksson, C.-J.; Mold, J. E.; Michaelsson, J.; Kuipers, J.; Beerenwinkel, N.

doi:10.1101/2025.02.28.640740

bioRxiv · 10.1101/2025.02.28.640740

Cell lineage inference from mitochondrial mutations

Hard, J.·Seidel, S.·Ferreira, P.·Berkes, P.·Jahn, K.·Eriksson, C.-J.·Mold, J. E.·Michaelsson, J.·Kuipers, J.·Beerenwinkel, N.

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Abstract

Tracing genealogical relationships between cells and their molecular states is essential for understanding tissue development, maintenance and disease. We present mt-SCITE, a computational method that reconstructs cell division histories from mitochondrial mutations in single cells. On simulated and experimental benchmarks, mt-SCITE outperformed existing methods in terms of cell lineage reconstruction, and scaled to thousands of cells. Applied to expanded CD8+ T cells following vaccination, mt-SCITE resolved subclonal relationships and revealed clones with predominantly memory-like, effector-like, or mixed states. mt-SCITE robustly identifies clonally related populations and resolves substructure within them, providing a broadly applicable approach to study cell lineage development.

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Hard, J., Seidel, S., Ferreira, P., Berkes, P., Jahn, K., Eriksson, C.-J., Mold, J. E., Michaelsson, J., Kuipers, J., Beerenwinkel, N.. 2025-03-05. Cell lineage inference from mitochondrial mutations. https://doi.org/10.1101/2025.02.28.640740

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