Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells.
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.
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Brussels B-1070, Belgium;
Aline
A
Wuidart
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Brussels B-1070, Belgium;
Marielle
M
Ousset
Cavendish Laboratory, Department of Physics, University of Cambridge Cambridge CB3 0HE, United Kingdom; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 1QN, United Kingdom; The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom; Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, United Kingdom;
Steffen
S
Rulands
Cavendish Laboratory, Department of Physics, University of Cambridge Cambridge CB3 0HE, United Kingdom; The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom; Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, United Kingdom;
Benjamin D
BD
Simons
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Brussels B-1070, Belgium;
Alexandra
A
Van Keymeulen
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Brussels B-1070, Belgium; Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Université Libre de Bruxelles, Brussels B-1070, Belgium.
Cédric
C
Blanpain
D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D003584:Cytological Techniques / Q000379:methods* / Q000592:standards; D003627:Data Interpretation, Statistical; D005260:Female; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000502:physiology; D011467:Prostate / Q000166:cytology* / Q000254:growth & development; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
mammary gland; multipotency; progenitor; prostate; stem cell; unipotency