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Updated: Mar 27, 2026

Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM

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Age-dependent Phylodynamics with Application to Single-cell Lineage Trees.

Nicola Mulberry^1,2, Julia Pilarski^1,2, Jana Dinger¹

¹Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.

Molecular Biology and Evolution

|March 26, 2026

Summary

New phylodynamic models account for cell division timing in development. This age-dependent approach corrects biases in previous studies of stem cell colonies and arthropod development.

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Area of Science:

Developmental Biology
Computational Biology
Phylogenetics

Background:

Phylogenetic and phylodynamic tools are increasingly used for single-cell lineage tracing in development.
Traditional phylodynamic methods, like the birth-death model, have assumptions not well-suited for developmental contexts.

Purpose of the Study:

To generalize the birth-death phylodynamic model to an age-dependent model for developmental studies.
To address limitations of existing phylodynamic methods in capturing key features of cell development.

Main Methods:

Developed a novel age-dependent phylodynamic model, a generalization of the birth-death model.
Applied the new model to public datasets of stem cell colonies and arthropod limb development.

Main Results:

Demonstrated that cell lineage trees in development deviate from birth-death model predictions due to characteristic generation times.
Showed that previous population-dynamic parameter estimates were biased by the birth-death tree prior.
Identified age-dependence as a common feature in developmental processes.

Conclusions:

The age-dependent phylodynamic model accurately captures developmental cell division patterns.
This framework offers a more robust approach for analyzing biological systems where birth-death assumptions are violated.
The method is available as a BEAST2 package for broader application.