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Related Experiment Video

Updated: Aug 20, 2025

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

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Published on: May 8, 2020

Quantitative fate mapping: A general framework for analyzing progenitor state dynamics via retrospective lineage

Weixiang Fang¹, Claire M Bell², Abel Sapirstein³

¹Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

|November 24, 2022

Summary

This study introduces quantitative fate mapping to reconstruct cell development dynamics using lineage barcodes. This method reveals progenitor cell hierarchy, timing, and biases, offering insights into developmental processes.

Keywords:

ICE-FASE Phylotime clonal dynamics coalescent theory homing CRISPR MARC1 barcoding phylogenetic inference progenitor field dynamics single cell ineage tracing somatic mutations time-scaled cell phylogeny

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Area of Science:

Developmental Biology
Genomics
Computational Biology

Background:

Somatic mutations in the genome record cellular phylogenetic relationships during development.
Understanding progenitor cell dynamics and their commitment biases remains a challenge.

Purpose of the Study:

To develop a quantitative fate mapping approach for reconstructing progenitor cell states and dynamics.
To introduce Phylotime, a scalable method for reconstructing time-scaled phylogenies from lineage barcodes.

Main Methods:

Quantitative fate mapping based on time-scaled phylogenies of descendant cells.
Phylotime: a scalable maximum likelihood clustering approach using a barcoding mutagenesis model.
Validation using in silico and in vitro barcoding experiments.

Main Results:

Reconstruction of progenitor cell hierarchy, commitment times, population sizes, and biases.
Establishment of criteria for robust quantitative fate mapping and progenitor state coverage.
Demonstration of lineage barcodes for analyzing post-embryonic progenitor fate.

Conclusions:

Quantitative fate mapping provides a powerful framework for studying developmental dynamics.
Lineage barcodes, natural or synthetic, are valuable tools for understanding cell fate and dynamics across organisms.
The Phylotime method enables scalable phylogenetic reconstruction from barcoding data.