Perie, Leila and Hodgkin, Philip D. and Naik, Shalin H. and Schumacher, Ton N. and de Boer, Rob J. and Duffy, Ken R. (2014) Determining Lineage Pathways from Cellular Barcoding Experiments. Cell Reports, 6. pp. 617-624. ISSN 2211-1247

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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.

Item Type:	Article
Additional Information:	This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. We thank T. Krohn for helpful feedback on the manuscript and L. Riboli-Sasco for useful discussions. L.P. was supported by a Marie Curie Intra European FP7 fellowship and a Bettencourt-Schueller foundation award. The work of P.H., S.N., T.S., and K.D. was supported by Human Frontier Science Program grant RGP0060/2012. R.D.B. and T.S. were supported by a Nederlandse Organisatie voor Wetenschappelijk Onderzoek TOPGOgrant (TOPGO.L.10.042). K.D. was also supported by Science Foundation Ireland grant 12 IP 1263. This research was supported in part by the National Science Foundation under grant NSF PHY11-25915 from the Kavli Institute for Theoretical Physics.
Keywords:	Lineage Pathways; Cellular Barcoding Experiments; barcoded data;
Academic Unit:	Faculty of Science and Engineering > Research Institutes > Hamilton Institute
Item ID:	5966
Depositing User:	Dr Ken Duffy
Date Deposited:	13 Mar 2015 15:28
Journal or Publication Title:	Cell Reports
Publisher:	Cell Press
Refereed:	Yes
Funders:	Science Foundation Ireland (SFI)
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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