Mature fibroblast cells can be reprogrammed, in vitro, to acquire stemness or pluripotency by transfecting them with transcription factors such as the Oct-4, Sox2, c-Myc and Klf4. However, in vivo, mature cells may dedifferentiate during development, or to facilitate tissue maintenance, and this occurs in the absence of exogenous biochemical factors. Roy et al show that fibroblasts can be reprogrammed to acquire pluripotency by confining them to a defined geometry, which is achieved by culturing cells on ECM coated micropatterned substrates. The cells, left to develop into a spheroid over 10 days, exhibited an increase in nuclear plasticity and chromatin reorganization, with a reduction in the level of H3K9Ac at mesenchymal promoters and a subsequent reduction in the expression of mesenchymal genes at day 6. The expression of stem cell specific genes such as Oct 4 and Sox2 increased at day 6, before being maximally expressed at day 10. To show the differentiation potential of the spheroids, the cells were directed into either endoderm or neuro-ectoderm linages using the respective differentiation media.