New techniques to assess the fate of stem cells in vivo
Stem cells ensure the development of tissues, their daily maintenance and their repair following injuries. One of the key questions in the field of stem cell biology is to define the different cell lineages in which stem cells can differentiate into. Stem cells can be multipotent, meaning they present the ability to give rise to more than one lineage, or unipotent, meaning they can only differentiate into one cell lineage. Lineage tracing experiments are routinely used in the fields of developmental and stem cell biology to assess the fate of stem cells in vivo. However, no rigorous method has yet been established to interpret with great precision and statistical confidence the issue of multipotency versus unipotency in lineage tracing experiments.
In a study that makes the cover of the current issue of Genes & Development, researchers from the ULB Cancer Research Center, U-CRC, led by Cédric Blanpain, MD/PhD, WELBIO investigator and Professor at the Faculty of Medicine, Université libre de Bruxelles, Belgium, developed new methods to assess with great precision the multipotent or unipotent fate of mammary gland and prostate stem cells.
Aline Wuidart and colleagues developed two novel methods to determine whether stem cells in the mammary gland and in the prostate are multipotent or unipotent during development and adult maintenance. In collaboration with physicists of the University of Cambridge, they developed a novel bio-statistical framework to define multipotency with high confidence in multicolor lineage tracing experiments. They developed another method called lineage tracing at saturation to assess the fate of all stem cells in a given tissue and the flux of cells between different lineages. "It was really important to sort out the issue of multipotency of mammary and prostate stem cells in a definitive manner. These novel and powerful tools combining multicolor lineage tracing, bio-statistical analysis and lineage tracing at saturation will allow to interpret the lineage experiments with much greater confidence", comments Aline Wuidart, the first author of this study.
These new findings unambiguously demonstrate that, while the prostate develops from multipotent stem cells, only unipotent stem cells mediate mammary gland development and adult tissue remodeling. "These methods offer a rigorous framework to assess the lineage relationship and stem cell fate in different organs and tissues. These techniques will become the new standard to decipher the lineage relationship in many other organs or tissues during development, tissue repair and tumor initiation." comments Cédric Blanpain, the senior author of the Genes & Development paper.