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

• Published in: Genes & development Vol. 30; no. 11; pp. 1261 - 1277
• Main Authors: Wuidart, Aline, Ousset, Marielle, Rulands, Steffen, Simons, Benjamin D., Van Keymeulen, Alexandra, Blanpain, Cédric
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.06.2016
• Subjects: Animals; Cell Lineage; Cells, Cultured; Cellular Biology; Cytological Techniques - methods; Cytological Techniques - standards; Data Interpretation, Statistical; Development Biology; Female; Life Sciences; Male; Mammary Glands, Animal - cytology; Mammary Glands, Animal - growth & development; Mice; Morphogenesis; Multipotent Stem Cells - cytology; Multipotent Stem Cells - physiology; Prostate - cytology; Prostate - growth & development; Research Paper; Stem Cells - cytology; Stem Cells - physiology; progenitor; prostate; multipotency; mammary gland; stem cell; unipotency
• ISSN: 0890-9369; 1549-5477; 1549-5477
• DOI: 10.1101/gad.280057.116

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.