Polymorphic dynamics of ribosomal proteins gene expression during somatic cell reprogramming and their differentiation in to 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 it’s 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.

Discriminative feature of cells characterizes cell populations of interest by a small subset of genes

“…S7c, d). This suggests that a certain composition of ribosomal protein-coding genes is the critical factor in stem cell functions, such as self-renewal 24–26 , and supports their role in muscle regeneration 27 . In conclusion, DFC can extract a small set of genes that characterize the POI, including functional associations between genes.…”

Discriminative feature of cells characterizes cell populations of interest by a small subset of genes

“…In contrast, the POI has a ribosomal protein profile closest to that of lymphocytes (LYM), but the negative weight of Rpl34 appears to differentiate the POI from the lymphocyte population. Furthermore, these ribosomal proteincoding genes clearly captured the temporal changes after muscle injury in the POI (S9C and S9D Fig) . This suggests that some ribosomal protein-coding genes are the critical factor in stem cell functions, such as self-renewal [30][31][32], and supports their role in muscle regeneration [33].…”

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“…In contrast, the POI has a ribosomal protein profile closest to that of lymphocytes (LYM), but the negative weight of Rpl34 appears to differentiate the POI from the lymphocyte population. Furthermore, these ribosomal proteincoding genes clearly captured the temporal changes after muscle injury in the POI (S9C and S9D Fig) . This suggests that some ribosomal protein-coding genes are the critical factor in stem cell functions, such as self-renewal [30][31][32], and supports their role in muscle regeneration [33].…”