Should we build single-cell lineage trees from gene expression data?

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Should we build single-cell lineage trees from gene expression data?
Συγγραφείς:	Mulberry N; Department of Biosystems Science & Engineering, ETH Zürich, Basel 4058, Switzerland.; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland., Stadler T; Department of Biosystems Science & Engineering, ETH Zürich, Basel 4058, Switzerland.; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.
Πηγή:	Genetics [Genetics] 2026 Sep 02; Vol. 234 (1).
Τύπος έκδοσης:	Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Oxford University Press Country of Publication: United States NLM ID: 0374636 Publication Model: Print Cited Medium: Internet ISSN: 1943-2631 (Electronic) Linking ISSN: 00166731 NLM ISO Abbreviation: Genetics Subsets: MEDLINE
Imprint Name(s):	Publication: 2021- : [Oxford] : Oxford University Press Original Publication: Austin, Tex. [etc.]
Ιατρικοί όροι (MeSH):	Cell Lineage/genetics , Single-Cell Analysis/methods , Phylogeny* , Models, Genetic* , Transcriptome* , Gene Expression Profiling*, Single-Cell Gene Expression Analysis ; Animals
Περίληψη:	Gene expression data have been proposed as a natural single-cell lineage marker. Here, we critically examine the feasibility of reconstructing lineage trees from single-cell transcriptomic data using both modeling and empirical data. We first introduce a notion of neutrality for transcriptomic data, and then, under a model for neutral gene expression, establish theoretical bounds for accurate lineage tree reconstruction. Our findings indicate that reconstruction guarantees for even small trees or sub-trees require thousands of independent, neutral traits-a condition that is likely rarely met in practice due to the dominance of non-neutral developmental signals. Furthermore, errors introduced by measurement sampling have the potential to destroy any existing lineage signal. We conclude that gene expression data have limited potential as a natural lineage recorder and should not be used for phylogenetic lineage tree inference without further, rigorous validation. (© The Author(s) 2026. Published by Oxford University Press on behalf of The Genetics Society of America.)
Competing Interests:	Conflicts of interest: We declare no conflicts of interest.
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Grant Information:	101001077 European Research Council (ERC)
Contributed Indexing:	Keywords: gene expression; lineage trees; phylogeny; single-cell RNA sequencing
Molecular Sequence:	GEO GSE315827
Entry Date(s):	Date Created: 20260718 Date Completed: 20260902 Latest Revision: 20260918
Update Code:	20260919
PubMed Central ID:	PMC13535251
DOI:	10.1093/genetics/iyag187
PMID:	42470686
Βάση Δεδομένων:	MEDLINE

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ISSN:	1943-2631
DOI:	10.1093/genetics/iyag187