A role for SHIP in stem cell biology and transplantation

Inositol phospholipid signaling pathways have begun to emerge as important players in stem cell biology and bone marrow transplantation [1-4]. The SH2-containing Inositol Phosphatase (SHIP) is among the enzymes that can modify endogenous mammalian phosphoinositides. SHIP encodes an isoform specific to pluripotent stem (PS) cells [5,6] plays a role in hematopoietic stem (HS) cell biology [7,8] and allogeneic bone marrow (BM) transplantation [1,2,9,10]. Here I discuss our current understanding of the cell and molecular pathways that SHIP regulates that influence PS/HS cell biology and BM transplantation. Genetic models of SHIP-deficiency indicate this enzyme is a potential molecular target to enhance both autologous and allogeneic BM transplantation. Thus, strategies to reversibly target SHIP expression and their potential application to stem cell therapies and allogeneic BMT are also discussed.     

Pluripotent stem cell heterogeneity and the evolving role of proteomic technologies in stem cell biology

Stem cells represent obvious choices for regenerative medicine and are invaluable for studies of human development and drug testing. The proteomic landscape of pluripotent stem cells (PSCs), in particular, is not yet clearly defined; consequently, this field of research would greatly benefit from concerted efforts designed to better characterize these cells. In this concise review, we provide an overview of stem cell potency, highlight the types and practical implications of heterogeneity in PSCs and provide a detailed analysis of the current view of the pluripotent proteome in a unique resource for this rapidly evolving field. Our goal in this review is to provide specific insights into the current status of the known proteome of both mouse and human PSCs. This has been accomplished by integrating published data into a unified PSC proteome to facilitate the identification of proteins, which may be informative for the stem cell state as well as to reveal areas where our current view is limited. These analyses provide insight into the challenges faced in the proteomic analysis of PSCs and reveal one area--the cell surface subproteome--that would especially benefit from enhanced research efforts.     

A chemical approach to stem cell biology

Small molecule libraries have been used successfully to probe several biological systems. Recent work has translated these successes across to the field of stem cell biology. Stem cells hold promise for both modeling of early development as well as having therapeutic potential. Enhanced understanding of the molecular mechanisms that control stem cell fates as well as an improved ability to manipulate cell populations are required. Known mechanistic chemical compounds have been used with stem cells to accomplish these two goals. More recently, through the utilization of high fitness libraries in phenotype-based screens, several small molecules that control self-renewal and differentiation in stem cells have been identified. These small molecules provide useful chemical tools for both basic research and practical applications.     

Advancing stem cell biology toward stem cell therapeutics

Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of disease-specific articles, outlining the challenges surrounding the clinical translation of stem cell therapeutics.     

A role for neurotrophins in embryonic stem cell growth

Neurotrophins act on embryonic cells through TRK receptors to inhibit apoptosis by phosphorylation of AKT. In a recent paper in Nature Biotechnology, show that the presence of selected neurotrophins enables cloning of trypsinized single embryonic stem cells and potentially increases the availability and usefulness of these stem cells.     

Model systems in stem cell biology

Stem cell scientists and ethicists have focused intently on questions relevant to the developmental stage and developmental capacities of stem cells. Comparably less attention has been paid to an equally important set of questions about the nature of stem cells, their common characteristics, their non-negligible differences and their possible developmental species specificity. Answers to these questions are essential to the project of justly inferring anything about human stem cell biology from studies in non-human model systems--and so to the possibility of eventually developing human therapies based on stem cell biology. After introducing and discussing these questions, I conclude with a brief discussion of the creation of novel model systems in stem cell biology: human-to-animal embryonic chimeras. Such novel model systems may help to overcome obstacles to extrapolation, but they are also scientifically and ethically contentious.     

Human mesenchymal stem cell biology

This brief overview summarises the main characteristics of bone marrow mesenchymal stem cells and of adipose-derived stem cells: methods of obtention, phenotype, differentiation potential, hematopoiesis-supportive (stromal) capacity, and immunosuppressive properties. Two points are discussed in detail: 1) criteria for stemness: multipotency, self-renewal, plasticity, and 2) the repair mechanisms implicated in the different indications of cell therapy using these cells: reconstitution of the tissue functional compartment by repopulation consequent to proliferation and differentiation or reprogrammation, stromal effects by secretion of angiogenic, anti-apoptotic, anti-fibrogenic factors, molecules involved in the regulation of inflammation, etc.     

Understanding telomerase in cancer stem cell biology

Comment on: Vicente-Dueñas C, et al. Oncotarget 2012; Epub ahead of print; PMID:22408137.     

New advances in stem cell biology: A perspective from gametogenesis

Regeneration of adult tissues relies on a small population of adult stem cells located in a specialized microenvironment. The adult stem cells divide continuously to produce new stem cells, as well as differentiated daughter cells to replenish lost cells due to damage or aging. The molecular mechanisms controlling their ability to divide, self-renew and differentiate remain largely undiscovered. The Drosophila reproductive systems have proven to be excellent models to understand the basic mechanisms regulating stem cell function. This report summarizes some of the recent advances in this field that were presented at the 49(th) Drosophila Research Conference held in San Diego in April 2008.     

New advances in stem cell biology: A perspective from gametogenesis

Regeneration of adult tissues relies on a small population of adult stem cells located in a specialized microenvironment. The adult stem cells divide continuously to produce new stem cells, as well as differentiated daughter cells to replenish lost cells due to damage or aging. The molecular mechanisms controlling their ability to divide, self-renew and differentiate remain largely undiscovered. The Drosophila reproductive systems have proven to be excellent models to understand the basic mechanisms regulating stem cell function. This report summarizes some of the recent advances in this field that were presented at the 49th Drosophila Research Conference held in San Diego in April 2008.     

A role for immunology in invasion biology

Invasive species are of increasing conservation and economic concern, yet mechanisms underlying invasions remain poorly understood. We propose that variation in immune defences might help explain why only some introduced populations become invasive. Introduced species escape many of their native diseases, but also face novel pathogens that can induce costly, and sometimes deadly, immune responses in na?ve hosts. Therefore, favouring less resource-demanding and dangerous defence mechanisms and allocating a greater proportion of resources to growth and reproduction should favour invasion. Specifically, we argue that successful invaders should reduce costly systemic inflammatory responses, which are associated with fever and metabolic and behavioural changes, and rely more heavily on less expensive antibody-mediated immunity. Here we provide supporting arguments for this hypothesis and generate predictions that are testable using tools from the growing field of ecological immunology.     

A bridge between chemistry and biology

Chemical biology is an interdisciplinary field that is undergoing rapid expansion around the globe. Recently, the Japanese Society for Chemical Biology sponsored its inaugural scientific meeting to discuss research at the interface of chemistry and biology.     

Applications of genetically engineered human pluripotent stem cell reporters in cardiac stem cell biology

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