Project description:The placenta is considered one of the candidate cell sources in cellular therapeutics because of a large number of cells and heterogenous cell population with myogenic potentials. We first analyzed myogenic potential of cells obtained from six parts of the placenta, i.e., umbilical cord, amniotic epithelium, amniotic mesoderm, chorionic plate, villous chorion (chorion frondosum), , and decidua basalis. Implantation of placenta-derived cells into dystrophic muscles of immunodeficient mdx mice restored sarcolemmal expression of human dystrophin. Co-existence of human and murine nuclei in one myotube and presence of human dystrophin in murine myotube suggests that human dystrophin expression is due to cell fusion between host murine myocytes and implanted human cells. In vitro analysis revealed that cells derived from amniotic mesoderm, chorionic plate, ,and villous chorion efficiently transdifferentiate into myotubes. These cells fused to C2C12 murine myoblasts by in vitro co-culturing, and murine myoblasts start to express human dystrophin after fusion. These results demonstrate that placenta-derived cells, especially extraembryonic mesodermal cells, have a myogenic potential and regenerative capacity of skeletal muscle. Determination of cell specification with the gene chip analysis revealed that each placental cell has a distinct expression pattern. Keywords: Determination of cell specification
Project description:Even though urothelial cancer (UC) is the fourth common tumor type among males, progress in treatment development has been deficient. Pathological assessment provides the urologists with only a broad classification, complicated by frequent disagreement among pathologist and the co-existence of different grading systems. Consequently, there is a great need for an objective, reproducible and biologically relevant classification system to make treatment more efficient. In the present investigation we present a molecular taxonomy for UC stratification based on integrated genomics. We used gene expression profiles from 308 UC to define seven molecular subtypes using step-by-step partitions and a bootstrap approach. Results were validated in three independent and publically available data sets. The subtypes differ significantly with respect to expression of cell cycle genes, of receptor tyrosine kinases particularity FGFR3, ERBB2 (HER2), and EGFR, of an FGFR3 associated gene expression signature, of cytokaratins, and of cell adhesion genes. The subtypes also differ significantly with respect to FGFR3, PIK3CA, and TP53 mutations. The expression of key proteins was validated by IHC on TMA. A further inspection indicated that the subtypes could be reduced to four major types of UC; Urobasal/D-driven, Genomically unstable/E-driven, Evolved urobasal, and Basal/SCC like, with characteristic and highly divergent molecular phenotypes. We show that the molecular subtypes cut across pathological classification and that tumors classified as one subtype maintain their characteristic molecular phenotype irrespective of pathological stage and grade. Available data from the Drugbank database and the Cochrane central registry of controlled trials indicate that susceptibility to specific drugs is more likely to be associated with the molecular stratification than with pathological classification. The presented molecular taxonomy stratifies UC into subtypes with distinct molecular phenotypes and biological properties. We anticipate that the molecular taxonomy will be a useful tool in future clinical investigations. Total RNA from fresh-frozen resection samples of 308 urothelial carcinomas was hybridized to the Illumina HumanHT-12 V3.0 expression beadchip arrays (Illumina Inc) at the SCIBLU Genomics Centre at Lund University Sweden (http://www.lth.se/sciblu). Supplementary files: GSE32894_non-normalized_308UCsamples.txt file = Raw intensity values for 308 UC (urothelial tumor) samples subjected only to background correction. GSE32894_reps_normals_preprocess*.txt files = Descriptive details and non-normalized data for technical replicates and normal samples that were used only in the preprocessing of the data. This dataset partly overlaps with Series GSE32549. Names of the overlapping sample names are the same, but the title of each sample is unique to the hybridization.