// NATURE NEWS — SPAZIO & SCIENZA
Reply to: Artefacts in single-cell mtDNA analyses misinform phylogenies
Nature
volume 656, pages E32–E38 (2026) Cite this article
The Original Article was published on 19 August 2026
replying to: C. A. Lareau et al. Nature https://doi.org/10.1038/s41586-026-10777-0 (2026).
In the accompanying Comment, Lareau et al.1 raise two concerns regarding our downstream analytical approach for lineage tracing from data generated using the single-cell Regulatory Multiomics (transcriptomics and chromatin accessibility) with Deep Mitochondrial Mutation Profiling (ReDeeM) workflow2: (1) that the variant-calling workflow in the ReDeeM framework identifies mutations that are detected in one molecule per cell—regarded as ‘low support’; and (2) that these variants found in excess on the edges of mitochondrial DNA (mtDNA) molecules could be artefacts that lead to low-mean and high-connectedness (LMHC) mutations and distort lineage inference. However, we disagree with these interpretations. Here we present multiple lines of evidence to address these concerns, reinforce the robustness of our core conclusions, and discuss limitations and future directions of mitochondrial-based lineage tracing.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
Prices may be subject to local taxes which are calculated during checkout
This study used the previously published ReDeeM haematopoiesis dataset (GEO accession GSE219015).
Lareau, C. A., Chapman, M. S., Penter, L., Nawy, T. & Pe’er, D. Artefacts in single-cell mtDNA analyses misinform phylogenies. Nature https://doi.org/10.1038/s41586-026-10777-0 (2026).