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Cellular Reprogramming (cellular + reprogramming)
Selected AbstractsReprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome,DEVELOPMENTAL DYNAMICS, Issue 2 2007Maia L. Green Abstract Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2× 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain-specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal proteins and proteasome, and up-regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up-regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near-significant up-regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613,631, 2007. © 2007 Wiley-Liss, Inc. [source] Generation of endoderm-derived human induced pluripotent stem cells from primary hepatocytes,HEPATOLOGY, Issue 5 2010Hua Liu Recent advances in induced pluripotent stem (iPS) cell research have significantly changed our perspective on regenerative medicine. Patient-specific iPS cells have been derived not only for disease modeling but also as sources for cell replacement therapy. However, there have been insufficient data to prove that iPS cells are functionally equivalent to human embryonic stem (hES) cells or are safer than hES cells. There are several important issues that need to be addressed, and foremost are the safety and efficacy of human iPS cells of different origins. Human iPS cells have been derived mostly from cells originating from mesoderm and in a few cases from ectoderm. So far, there has been no report of endoderm,derived human iPS cells, and this has prevented comprehensive comparative investigations of the quality of human iPS cells of different origins. Here we show for the first time reprogramming of human endoderm-derived cells (i.e., primary hepatocytes) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from hES cells with respect to colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body formation and teratoma assays. In addition, these cells are able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes. Conclusion: The technology to develop endoderm,derived human iPS cell lines, together with other established cell lines, will provide a foundation for elucidating the mechanisms of cellular reprogramming and for studying the safety and efficacy of differentially originated human iPS cells for cell therapy. For the study of liver disease pathogenesis, this technology also provides a potentially more amenable system for generating liver disease-specific iPS cells. (HEPATOLOGY 2010;51:1810,1819) [source] Setting and resetting of epigenetic marks in malignant transformation and developmentBIOESSAYS, Issue 8 2010Holger Richly Abstract Epigenetic modifications, such as DNA methylation and post-translation modifications of histones, have been shown to play an important role in chromatin structure, promoter activity, and cellular reprogramming. Large protein complexes, such as Polycomb and trithorax, often harbor multiple activities which affect histone tail modification. Nevertheless, the mechanisms underlying the deposition of these marks, their propagation during cell replication, and the alteration on their distribution during transformation still require further study. Here we review recent data on those processes in both normal and cancer cells, and we propose that the unscheduled expression of oncogenic transcription factors causes reprogramming of normal cells into cancer stem cells. [source] Neural stem cells: Mechanisms of fate specification and nuclear reprogramming in regenerative medicineBIOTECHNOLOGY JOURNAL, Issue 12 2008Carsten W. Lederer Abstract Recently, intense interest in the potential use of neural stem cells (NSC) in the clinical therapy of brain disease and injury has resulted in rapid progress in research on the properties of NSC, their innate and directed differentiation potential and the induced reprogramming of differentiated somatic cells to revert to a pluripotent NSC-like state. The aim of this review is to give an overview of our current operational definitions of the NSC lineage, the growing understanding of extrinsic and intrinsic mechanisms, including heritable but reversible epigenetic chromatin modifications that regulate the maintenance and differentiation of NSC in vivo, and to emphasize ground-breaking efforts of cellular reprogramming with the view to generating patient-specific stem cells for cell replacement therapy. This is set against a summary of current practical procedures for the isolation, research and application of NSC, and of the state of the art in NSC-based regenerative medicine of the nervous system. Both provide the backdrop for the translation of recent findings into innovative clinical applications, with the hope of increasing the safety, efficiency and ethical acceptability of NSC-based therapies in the near future. [source] | ||||||||||