The Ontogeny of Somatic Stem Cells

Abstract

Cells in vertebrate tissues are richly diversified in their morphological, biochemical and functional characteristics. Understanding the generation of such an array of cell diversity from relatively few precursor cells continues to be a major research focus in the developmental and stem cell biology fields. The formation of a relatively complex vertebrate embryo from a simple ball or sheet of primitive cells in early development begins with the process of gastrulation [1]. What emerges during this epoch of development is an embryonic body plan with three separate germ layers: endoderm, mesoderm and ectoderm. These germ layers often appear cytologically indistinct yet among them are the primordial cells that will go on to generate the many distinct tissues of the body. We generally refer to these primordial cells as ‘tissuespecific’ or ‘somatic’ stem cells and we ascribe three main properties to them: self-renewal, tissue-specific multipotentiality, and longevity [2–4]. Major efforts towards defining the unique properties of somatic stem cells has yielded significant insight into the identity and behavior of these cells, in the form of stem cell specific markers and their lineage potential. Nonetheless, there are some fundamental questions that remain unanswered and we believe this knowledge gap lies at the heart of the challenge to translate what we know about stem cells into successful therapies or biotechnological applications. In this special issue of Stem Cell Reviews & Reports, we have asked some of the leading scientists in the developmental biology and stem cell biology fields to comment on a few of these fundamental questions, such as: where do stem cells come from; or, does stem cell behavior change over time, and if so how? These questions exemplify the notion of somatic stem cell ontogeny, which focuses on quantitative and/or qualitative differences in stem cell behavior through time and space. This concept is important for the simple reason that we need to know how fetal stem cells are initially generated in a given tissue, where they are located and whether they maintain the same properties and locations throughout life (e.g., reviews by L. Grabel, and Z. Burke and D. Tosh) [5, 6]. Somatic stem cell ontogeny is a concept that deals with some of stem cell biology’s more contemporary, and controversial, issues. For instance, the generative processes of somatic stem cells may serve quite distinct purposes at different life stages. Most scientists would agree that during embryogenesis, somatic stem cells have a major and widespread role in tissue formation, yet in adulthood these somatic stem cells are relatively quiescent and typically localized to rather tiny compartments within the same tissues they helped build. In some cases, it has been debated whether bona fide stem cells even exist in adult tissue compartments where they were once active during formative stages [7], while in other cases the debate centers on whether tissues developed to contain only a single stem cell or multiple distinct stem cells that persist in adulthood [8]. It is clear that individual tissues are impacted by predictable physiological variations in growth, maturation, reproduction, and V. Tropepe (*) Department of Cell & Systems Biology, University of Toronto, 25 Harbord Street, Toronto, ON M5S 3G5, Canada e-mail: v.tropepe@utoronto.ca