Adult stem cells versus induced pluripotent stem cells

Abstract

Recent findings on heterogeneity, flexibility and plasticity of stem cells are challenging the traditional concept of stem cells as pre-programmed entities. The concept of self-organizing systems offers an alternative, more elegant and comprehensive explanation for the experimental data. In recent decades, biological studies of stem cells have evolved a broad spectrum of phenomena, ranging from cellular level to tissue level, suggesting we need to abandon the classical concept of a rigid hierarchy of stem cells development and organization, in order to better understand the dynamic and functional issues involving these cells. This perspective has implications for the characterization of stem cells from specific tissues (for example, on gene expression profiles and patterns of gene regulation and epigenetic changes). The proposed project is composed of seven different sub-projects that aim to deeply investigate the current concept of adult stem cells niche using as a model: human immature dental pulp stem cells, described by our group. In addition, the project proposes to investigate the existence of pluripotent stem cell niche during embryonic and fetal development. We will also analyze how immature dental pulp stem cells will respond to environmental changes when reintroduced in a "strange-niche". Next, we will study the limits of pluripotency of both: mouse immature dental pulp stem cells, which have already been obtained by us, and induced pluripotent cells, originated from these mouse immature dental pulp stem cells by the method of chimeras generation and germ line transmission. Using cellular reprogramming tool, we will analyze morphological diversity that we observed after isolation of induced pluripotent cells clones from a single cell, focusing on genetic and epigenetic mechanisms, which are responsible for this diversity. Using this same tool, we intend to study reprogramming potential of tumorigenic cells by checking the decrease or loss of malignancy and to provide a model to investigate the control of cancer cells. Thus, this project is challenging and will contribute with scientific and technological results of high-impact to the advancement of stem cells biology. (AU)