Long-term in vitro, cell-type-specific genome-wide reprogramming of gene expression

Stress as a fundamental theme in cell plasticity

“…The question raised is whether the phenomena of dedifferentiation in mammalians occur only under such experimental conditions. In fact this does not seem to be the case since reprogramming has been documented following treatment of perforated cells by protein extracts [9,29,50]. Testis derived cells from mouse [26] or human [14,45] origin acquired differentiation potencies similar to ESCs without the need for harsh manipulations, such as those required for obtaining iPSCs.…”

Induction of Dedifferentiation, Genomewide Transcriptional Programming, and Epigenetic Reprogramming by Extracts of Carcinoma and Embryonic Stem Cells

“…The phenotype was not a mere consequence of treatment with any extract as 293T cells incubated in their own extract did not form colonies ( Figure 1B, f-j), and 293T cells treated with an extract of Jurkat cells formed clearly morphologically distinct aggregates ( Figure 1C). The latter were reminiscent of Jurkat T-cell clusters (Håkelien et al, 2005).…”

“…Notably, extracts of regenerating newt limbs promote cell cycle reentry and down-regulation of myogenic markers in differentiated myotubes (McGann et al, 2001). Furthermore, we have shown that kidney epithelial 293T cells permeabilized with streptolysin O (SLO) and briefly exposed to an extract of Jurkat T-cells take on T-cell properties, including growth in aggregates, chromatin remodeling, expression of T-cell-specific genes and surface receptors, secretion of interleukin-2, and stimulation-dependent assembly of the interleukin-2 receptor (Håkelien et al, , 2005Landsverk et al, 2002). Similarly, lysates of cardiomyocytes or insulinoma cells elicit expression of cardiomyocyte or ␤-cell markers in adipose stem cells and fibroblasts (Håkelien et al, 2004), and a pneumocyte extract was recently shown to induce differentiation of ESCs into a pneumocyte phenotype (Qin et al, 2005).…”

Generation of somatic cells by direct conversion: Do we need pluripotent cells?

“…This was followed by directed differentiation of pluripotent mouse ESCs into type II pneumocytes (8) and cardiomyocytes (7); however, expression of the genes upregulated by reprogramming was often tran-sient depending on the nature of the type of cell derived. Rat insuloma reprogrammed fibroblasts could only maintain Pdx1 and insulin gene expression for several days, although Jurkat cell extract treated 293T cells were able to maintain the new transcriptome over three months, albeit with progressive decreases in expression levels (9). This implies that the epigenetic reprogramming requirement for exogenous gene upregulation is not permanent.…”