Bayesian Phylogenetic Lineage Reconstruction with Loss of Heterozygosity Mutations Derived from Single-Cell RNA Sequencing

Donovan J Anderson; Marshall S Horwitz

doi:10.1007/978-1-0716-4310-5_1

Bayesian Phylogenetic Lineage Reconstruction with Loss of Heterozygosity Mutations Derived from Single-Cell RNA Sequencing

Methods Mol Biol. 2025:2886:1-22. doi: 10.1007/978-1-0716-4310-5_1.

Authors

Donovan J Anderson¹, Marshall S Horwitz²

Affiliations

¹ Allen Discovery Center for Lineage Tracing and Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA.
² Allen Discovery Center for Lineage Tracing and Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA. [email protected].

PMID: 39745633
DOI: 10.1007/978-1-0716-4310-5_1

Abstract

Mutations are acquired frequently, such t`hat each cell's genome inscribes its history of cell divisions. Loss of heterozygosity (LOH) accumulates throughout the genome, offering large encoding capacity for phylogenetic inference of cell lineage.In this chapter, we demonstrate a method, using single-cell RNA sequencing, for reconstructing cell lineages from inferred LOH events in a Bayesian manner, annotating the lineage with cell phenotypes, and marking developmental time points based on X-chromosome inactivation. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and was initially developed to investigate Emx1+ cortical projection neuron and glia lineages from C57Bl/6J (B6) and CAST/EiJ (CA) interstrain F1 mice, describing progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis.

Keywords: Bayesian; Cell lineage; Development; LOH; Loss of heterozygosity; Method; Phylogeny; Single cell; X-inactivation.

MeSH terms

Animals
Bayes Theorem*
Cell Lineage* / genetics
Loss of Heterozygosity*
Mice
Mice, Inbred C57BL
Mutation
Neurons / cytology
Neurons / metabolism
Phylogeny*
Sequence Analysis, RNA / methods
Single-Cell Analysis* / methods
X Chromosome Inactivation / genetics