Reprogrammed cells harbour chromosomal structural signature of cellular origin

17 March 2015

Scientists at the Hubrecht Institute have discovered that IPSCs receive a chromosomal structural signature of the cellular origin when they are reprogrammed. These signatures allow the cell of origin to be determined, although these signatures were not present in the original source cell types. The study is published in Cell Stem Cell this week.

Induced pluripotent stem cells (iPSCs) are stem cells that are generated from somatic cells. These iPSCs have the ability to contribute to all tissues, which makes them attractive for disease modelling and regenerative medicine. Many different somatic cell types can be reprogrammed to iPSCs. However, they retain a memory of their cell type origin such that differentiation propensity of iPSCs reflects the tissue of origin.

To better understand somatic cell reprogramming and the molecular differences between iPSCs derived from different cell types, scientists at the Hubrecht Institute and CRG in Barcelona investigated how genes that are responsible for somatic cell function are turned off and genes important for stem cell function are turned on. They did this by studying the three-dimensional structure of the genome and how this is affected during reprogramming. By comparing the 3D genome in somatic cells, iPSCs derived from these somatic cells and ESCs, Krijger et al. report that somatic cell reprogramming is accompanied by massive changes in genome folding, which, irrespective of the cell type of origin, converge on the 3D structure of the pluripotent genome. Despite this, distinct topological features separate early passage iPSCs according to their cell type of origin and these differences seem to be acquired during reprogramming in a founder cell-dependent manner.

This study demonstrates that iPSCs derived from different somatic cell types have distinct transcriptional and genome topology features. Different somatic cell types may thus follow specific reprogramming trajectories. Future research must be done to uncover the molecular basis of the correlation between the reprogramming trajectories, tissue-specific gene expression signatures, and genome topologies in the different cell of origin-derived iPSCs.

Article: http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)00008-4