Reconstructing Progenitor State Hierarchy and Dynamics Using Lineage Barcoding Data

Weixiang Fang; Yi Yang; Hongkai Ji; Reza Kalhor

doi:10.1007/978-1-0716-4310-5_9

Reconstructing Progenitor State Hierarchy and Dynamics Using Lineage Barcoding Data

Methods Mol Biol. 2025:2886:177-199. doi: 10.1007/978-1-0716-4310-5_9.

Authors

Weixiang Fang^{1

2}, Yi Yang^{1

2}, Hongkai Ji³, Reza Kalhor^{4

5

6}

Affiliations

¹ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
⁵ Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].
⁶ Departments of Molecular Biology & Genetics, Medicine, Neuroscience, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. [email protected].

PMID: 39745641
DOI: 10.1007/978-1-0716-4310-5_9

Abstract

Measurements of cell phylogeny based on natural or induced mutations, known as lineage barcodes, in conjunction with molecular phenotype have become increasingly feasible for a large number of single cells. In this chapter, we delve into Quantitative Fate Mapping (QFM) and its computational pipeline, which enables the interrogation of the dynamics of progenitor cells and their fate restriction during development. The methods described here include inferring cell phylogeny with the Phylotime model, and reconstructing progenitor state hierarchy, commitment time, population size, and commitment bias with the ICE-FASE algorithm. Evaluation of adequate sampling based on progenitor state coverage statistics is emphasized for interpreting the QFM results. Overall, this chapter describes a general framework for characterizing the dynamics of cell fate changes using lineage barcoding data.

Keywords: ICE-FASE; Lineage barcoding pipeline; Lineage tracing; Phylotime; Progenitor state dynamics; Quantitative fate mapping (QFM); Time-scaled cell phylogeny.

MeSH terms

Algorithms*
Animals
Cell Differentiation / genetics
Cell Lineage* / genetics
Computational Biology / methods
DNA Barcoding, Taxonomic / methods
Humans
Phylogeny
Single-Cell Analysis / methods
Software
Stem Cells / cytology
Stem Cells / metabolism