Reconstructing Progenitor State Hierarchy and Dynamics Using Lineage Barcoding Data.

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.