Stem cell clonality -- theoretical concepts, experimental techniques, and clinical challenges

Here we report highlights of discussions and results presented at an International Workshop on Concepts and Models of Stem Cell Organization held on July 16th and 17th, 2012 in Dresden, Germany. The goal of the workshop was to undertake a systematic survey of state-of-the-art methods and results of clonality studies of tissue regeneration and maintenance with a particular emphasis on the hematopoietic system. The meeting was the 6th in a series of similar conceptual workshops, termed StemCellMathLab,(2) all of which have had the general objective of using an interdisciplinary approach to discuss specific aspects of stem cell biology. The StemCellMathLab 2012, which was jointly organized by the Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Dresden University of Technology and the Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, brought together 32 scientists from 8 countries, with scientific backgrounds in medicine, cell biology, virology, physics, computer sciences, bioinformatics and mathematics. The workshop focused on the following questions: (1) How heterogeneous are stem cells and their progeny? and (2) What are the characteristic differences in the clonal dynamics between physiological and pathophysiological situations? In discussing these questions, particular emphasis was placed on (a) the methods for quantifying clones and their dynamics in experimental and clinical settings and (b) general concepts and models for their description. In this workshop summary we start with an introduction to the current state of clonality research and a proposal for clearly defined terminology. Major topics of discussion include clonal heterogeneity in unperturbed tissues, clonal dynamics due to physiological and pathophysiological pressures and conceptual and technical issues of clone quantification. We conclude that an interactive cross-disciplinary approach to research in this field will continue to promote a conceptual understanding of tissue organization.