🙏 Thanks to @caleblareau.bsky.social l, @hattaca.bsky.social, @helenaradbruch.bsky.social ky.social, Benedikt Obermayer, Marie Cotta, Frank Hepper, David Capper, Wolfram Kunz, Markus Schülke & all team members for their contributions!

Together, scmtMPM & scwMSS provide a quantitative framework for somatic mtDNA mosaicism, advancing mitochondrial genetics & disease research.

Using POLG-mutant cells, healthy donors & patients, we show:
🔹 Complex single-cell mutational landscapes
🔹 Negative selection against truncating & pathogenic variants

🔹 Constrained mutations in Complex I

🔥 Our second preprint, led by Josch, introduces a new framework to measure mtDNA mutational burden & constraint at single-cell resolution.
We present:
🔹 scmtMPM (mutations per Mb)
🔹 scwMSS (heteroplasmy-weighted local constraint)
👉 www.researchsquare.com/article/rs-6...

In short: Cryo-mtscATAC-seq enables cell state–informed clonality from frozen specimens, opening new avenues to leverage biobanked tissue in health & disease.

Cryo-mtscATAC-seq + our mitoBender computational tool:
🔹 Works on archival frozen tissue
🔹 Extends mtDNA genotyping to brain, glioblastoma, neuroblastoma & vascular tissue
🔹 Reveals clonal gliogenesis, microglial expansions, chemo-induced heterogeneity & smooth muscle oligoclonality