title: Determining lineage pathways from cellular barcoding experiments.
abstract: Cellular barcoding and other single-cell lineage-tracing strategies form experimental methodologies for analysis of in vivo cell fate that have been instrumental in several significant recent discoveries. Due to the highly nonlinear nature of proliferation and differentiation, interrogation of the resulting data for evaluation of potential lineage pathways requires a new quantitative framework complete with appropriate statistical tests. Here, we develop such a framework, illustrating its utility by analyzing data from barcoded multipotent cells of the blood system. This application demonstrates that the data require additional paths beyond those found in the classical model, which leads us to propose that hematopoietic differentiation follows a loss of potential mechanism and to suggest further experiments to test this deduction. Our quantitative framework can evaluate the compatibility of lineage trees with barcoded data from any proliferating and differentiating cell system.
authors: Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, the Netherlands. Electronic address: l.perie@nki.nl.
authors: Leïla
authors: L
authors: Perié
authors: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Philip D
authors: PD
authors: Hodgkin
authors: Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Shalin H
authors: SH
authors: Naik
authors: Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
authors: Ton N
authors: TN
authors: Schumacher
authors: Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, the Netherlands.
authors: Rob J
authors: RJ
authors: de Boer
authors: Hamilton Institute, National University of Ireland, Maynooth, Ireland.
authors: Ken R
authors: KR
authors: Duffy
mesh_terms: D000818:Animals; D019070:Cell Lineage; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D008954:Models, Biological