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Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells.

Published version
Peer-reviewed

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Authors

Wuidart, Aline 
Ousset, Marielle 
Simons, Benjamin D 
Van Keymeulen, Alexandra 

Abstract

Lineage tracing has become the method of choice to study the fate and dynamics of stem cells (SCs) during development, homeostasis, and regeneration. However, transgenic and knock-in Cre drivers used to perform lineage tracing experiments are often dynamically, temporally, and heterogeneously expressed, leading to the initial labeling of different cell types and thereby complicating their interpretation. Here, we developed two methods: the first one based on statistical analysis of multicolor lineage tracing, allowing the definition of multipotency potential to be achieved with high confidence, and the second one based on lineage tracing at saturation to assess the fate of all SCs within a given lineage and the "flux" of cells between different lineages. Our analysis clearly shows that, whereas the prostate develops from multipotent SCs, only unipotent SCs mediate mammary gland (MG) development and adult tissue remodeling. These methods offer a rigorous framework to assess the lineage relationship and SC fate in different organs and tissues.

Description

Keywords

mammary gland, multipotency, progenitor, prostate, stem cell, unipotency, Animals, Cell Lineage, Cells, Cultured, Cytological Techniques, Data Interpretation, Statistical, Female, Male, Mammary Glands, Animal, Mice, Multipotent Stem Cells, Prostate, Stem Cells

Journal Title

Genes Dev

Conference Name

Journal ISSN

0890-9369
1549-5477

Volume Title

30

Publisher

Cold Spring Harbor Laboratory
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Medical Research Council (MC_PC_12009)
WELBIO