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Updated: Aug 6, 2026
10:12
Droplet Barcoding-Based Single Cell Transcriptomics of Adult Mammalian Tissues
Published on: January 10, 2019
Should we build single-cell lineage trees from gene expression data?
Nicola Mulberry1,2, Tanja Stadler1,2
1Department of Biosystems Science & Engineering, ETH Zurich, 4058 Basel, Switzerland.
Genetics
|July 18, 2026
Summary
Single-cell gene expression data is unlikely to accurately reconstruct lineage trees. Thousands of neutral traits are needed, which are rare due to developmental signals and measurement errors, limiting its use in phylogenetics.
Area of Science:
- Computational Biology
- Genomics
- Developmental Biology
Background:
- Single-cell gene expression data is a proposed marker for tracing cell lineages.
- Reconstructing lineage trees is crucial for understanding developmental processes and evolutionary history.
Purpose of the Study:
- To critically evaluate the feasibility of using single-cell transcriptomic data for lineage tree reconstruction.
- To establish theoretical limits for accurate lineage reconstruction based on gene expression data.
Main Methods:
- Development of a neutrality concept for transcriptomic data.
- Application of a neutral gene expression model to establish theoretical reconstruction bounds.
- Analysis of empirical data to assess practical limitations.
Main Results:
- Accurate lineage tree reconstruction requires thousands of independent, neutral genetic traits.
- Non-neutral developmental signals frequently dominate gene expression, violating neutrality assumptions.
- Measurement sampling errors can significantly degrade or eliminate lineage information.
Conclusions:
- Single-cell gene expression data has limited utility as a natural lineage recorder.
- Phylogenetic lineage tree inference using gene expression data requires substantial validation due to inherent limitations.
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