http://www.mdpi.com/journal/genes/special_issues/pluripotency-Scells/ Dear Colleagues, Cellular pluripotency is one of the most fascinating and promising research fields in biomedical research. The recent discovery that ordinary cells following the introduction of a small number of genes can acquire stem cell behaviors opens a new door for stem cell research and its application to therapeutic discovery. The exhaustive understanding of the molecular pathways controlling pluripotency and cellular reprogramming is essential for the development of effective and safe approaches to reprogram somatic cells towards a pluripotent state. This Special Issue of the Journal Genes aims at presenting recent research and developments on this very exciting topic. Reviews and original papers presenting data on embryonic and induced pluripotent stem cells are welcome for this Special Issue. Special interest will be given to reports on genes and/or pathways involved in the establishment and maintenance of natural and acquired pluripotency, in controlling the global and local chromatin organization in pluripotent cells, and in triggering reprogramming in somatic and adult stem cells. Dr. Paolo Cinelli Guest Editor Related Special Issue Cancer Stem Cells in Cancers {snippet name="submission_info"} http://www.mdpi.com/2073-4425/2/1/280/ Developmental biology, regenerative medicine and cancer biology are more and more interested in understanding the molecular mechanisms controlling pluripotency and self-renewal in stem cells. Pluripotency is maintained by a synergistic interplay between extrinsic stimuli and intrinsic circuitries, which allow sustainment of the undifferentiated and self-renewing state. Nevertheless, even though a lot of efforts have been made in the past years, the precise mechanisms regulating these processes remain unclear. One of the key extrinsic factors is leukemia inhibitory factor (LIF) that is largely used for the cultivation and derivation of mouse embryonic and induced pluripotent stem cells. LIF acts through the LIFR/gp130 receptor and activates STAT3, an important regulator of mouse embryonic stem cell self-renewal. STAT3 is known to inhibit differentiation into both mesoderm and endoderm lineages by preventing the activation of lineage-specific differentiation programs. However, LIF activates also parallel circuitries like the PI3K-pathway and the MEK/ERK-pathway, but its mechanisms of action remain to be better elucidated. This review article aims at summarizing the actual knowledge on the importance of LIF in the maintenance of pluripotency and self-renewal in embryonic and induced pluripotent stem cells. http://www.mdpi.com/2073-4425/2/1/280/ Wed, 09 Mar 2011 00:00:00 CET Genes 2011-03-09 2 1 Review 280 297 2073-4425 The Role of the Leukemia Inhibitory Factor (LIF) — Pathway in Derivation and Maintenance of Murine Pluripotent Stem Cells 2011-03-09 doi: 10.3390/genes2010280 Urs Graf Elisa A. Casanova Paolo Cinelli http://www.mdpi.com/2073-4425/2/1/229/ E-cadherin; pluripotency; embryonic stem cell; induced pluripotent stem cell; iPS; ES; signaling pathways; Activin; Nodal http://www.mdpi.com/2073-4425/2/1/229/ Fri, 25 Feb 2011 00:00:00 CET Genes 2011-02-25 2 1 Review 229 259 2073-4425 The Function of E-Cadherin in Stem Cell Pluripotency and Self-Renewal 2011-02-25 doi: 10.3390/genes2010229 Francesca Soncin Christopher M. Ward http://www.mdpi.com/2073-4425/2/1/107/ Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunological, and ethical problems. Recent studies have revealed that NSCs also reside in the adult brain. The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems. Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine. http://www.mdpi.com/2073-4425/2/1/107/ Fri, 14 Jan 2011 00:00:00 CET Genes 2011-01-14 2 1 Review 107 130 2073-4425 Prospects and Limitations of Using Endogenous Neural Stem Cells for Brain Regeneration 2011-01-14 doi: 10.3390/genes2010107 Naoko Kaneko Eisuke Kako Kazunobu Sawamoto http://www.mdpi.com/2073-4425/2/1/81/ The dramatic discovery that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs), by the expression of just four factors, has opened new opportunities for regenerative medicine and novel ways of modeling human diseases. Extensive research over the short time since the first iPSCs were generated has yielded the ability to reprogram various cell types using a diverse range of methods. However the duration, efficiency, and safety of induced reprogramming have remained a persistent limitation to achieving a robust experimental and therapeutic system. The field has worked to resolve these issues through technological advances using non-integrative approaches, factor replacement or complementation with microRNA, shRNA and drugs. Despite these advances, the molecular mechanisms underlying the reprogramming process remain poorly understood. Recently, through the use of inducible secondary reprogramming systems, researchers have now accessed more rigorous mechanistic experiments to decipher this complex process. In this review we will discuss some of the major recent findings in reprogramming, pertaining to proliferation and cellular senescence, epigenetic and chromatin remodeling, and other complex cellular processes such as morphological changes and mesenchymal-to-epithelial transition. We will focus on the implications of this work in the construction of a mechanistic understanding of reprogramming and discuss unexplored areas in this rapidly expanding field. http://www.mdpi.com/2073-4425/2/1/81/ Thu, 13 Jan 2011 00:00:00 CET Genes 2011-01-13 2 1 Review 81 106 2073-4425 Looking into the Black Box: Insights into the Mechanisms of Somatic Cell Reprogramming 2011-01-13 doi: 10.3390/genes2010081 Laurent David Payman Samavarchi-Tehrani Azadeh Golipour Jeffrey L. Wrana http://www.mdpi.com/2073-4425/1/3/413/ Xenopus embryos provide a rich source of pluripotent cells that can be differentiated into functional organs. Since the molecular principles of vertebrate organogenesis appear to be conserved between Xenopus and mammals, this system can provide useful guidelines for the directional manipulation of human embryonic stem cells. Pluripotent Xenopus cells can be easily isolated from the animal pole of blastula stage Xenopus embryos. These so called “animal cap” cells represent prospective ectodermal cells, but give rise to endodermal, mesodermal and neuro-ectodermal derivatives if treated with the appropriate factors. These factors include evolutionary conserved modulators of the key developmental signal transduction pathways that can be supplied either by mRNA microinjection or direct application of recombinant proteins. This relatively simple system has added to our understanding of pancreas, liver, kidney, eye and heart development. In particular, recent studies have used animal cap cells to generate ectopic eyes and hearts, setting the stage for future work aimed at programming pluripotent cells for regenerative medicine. http://www.mdpi.com/2073-4425/1/3/413/ Thu, 18 Nov 2010 00:00:00 CET Genes 2010-11-18 1 3 Review 413 426 2073-4425 Programming Pluripotent Precursor Cells Derived from Xenopus Embryos to Generate Specific Tissues and Organs 2010-11-18 doi: 10.3390/genes1030413 Annette Borchers Tomas Pieler http://www.mdpi.com/2073-4425/1/1/4/ Embryonic stem cells (ESCs) and induced pluripotent stem cells (IPSCs) hold great promise for the therapeutic treatment of human diseases, but their functional similarity, their stability and especially the mechanism underlying their derivation are not yet clearly explained. [...] http://www.mdpi.com/2073-4425/1/1/4/ Tue, 09 Mar 2010 00:00:00 CET Genes 2010-03-09 1 1 Editorial 4 8 2073-4425 The Secret Lives of Pluripotent Cells: There and Back Again 2010-03-09 doi: 10.3390/genes1010004 Paolo Cinelli