Polymorphic dynamics of ribosomal proteins gene expression during somatic cell reprogramming and their differentiation into specialized cells-types

Abstract

Factor induced pluripotent stem cells (iPSCs) offer great promise in regenerative medicine. However, accumulating evidence suggests that iPSCs are heterogeneous in comparison with embryonic stem cells (ESCs), and that is attributed to various genetic and epigenetic states of donor cells. In the light of the discovery of cell-type specialized ribosomal protein composition, its role as the cells transit through different stages of reprogramming and when iPSCs differentiate into specialized cell-types has not been explored to understand its influence in the reprogramming and differentiation process and outcome. By re-analyzing the publicly available gene expression datasets among ESCs, various sources of iPSCs and somatic cells and by studying the ribosomal protein gene expression during different stages of reprogramming of somatic cells and different passages of established iPSCs we found distinct patterns of their expression across multiple cell-types. We experimentally validated these results on the cells undergoing reprogramming from human dermal fibroblasts. Finally, by comparing publicly available data from iPSCs, iPSCs derived specialized cells and its in vivo counterparts, we show alterations in ribosomal gene expression during differentiation of specialized cells from iPSCs which may have Implications in the context of ribosomopathies. Our results provide an informatics framework for researchers in efficient generation of iPSCs that are equivalent to ESCs.