Abstract: Novel methods are herein provided for high-throughput, dual analysis of DNA methylation and gene expression, and triple analysis of DNA methylation, gene expression and gene-associated histone acetylation in cancer cells using arrayed expressed CpG island sequence tags (ECISTs). ECISTs correspond to genomic DNA fragments comprising GC-rich segments along with promoter and/or exon (e.g., first exon) portions of genes. The GC-rich segments are useful for screening hypermethylated CpG sites in cancer cells, while the corresponding promoter and exon-containing portions are useful for determining corresponding transcript levels and assessing histone acetylation. Also provided are high-throughput methods for either confirming methylation-dependent gene silencing, or identifying therapeutically effective demethylating agents, using the ECIST array panels to identify hypermethylated loci, and measure expression levels thereof after cellular exposure to demethylating agents.

Abstract: A composition comprising a plurality of cell aggregates for use in the production of engineered organotypic tissue by organ printing. A method of making a plurality of cell aggregates comprises centrifuging a cell suspension to form a pellet, extruding the pellet through an orifice, and cutting the extruded pellet into pieces. Apparatus for making cell aggregates comprises an extrusion system and a cutting system. In a method of organ printing, a plurality of cell aggregates are embedded in a polymeric or gel matrix and allowed to fuse to form a desired three-dimensional tissue structure. An intermediate product comprises at least one layer of matrix and a plurality of cell aggregates embedded therein in a predetermined pattern. Modeling methods predict the structural evolution of fusing cell aggregates for combinations of cell type, matrix, and embedding patterns to enable selection of organ printing processes parameters for use in producing an engineered tissue having a desired three-dimensional structure.