Identifying Candidate Reprogramming Genes in Mouse Induced Pluripotent Stem Cells

Jan 8, 2017Stem cell reviews and reports

Finding Genes That May Help Turn Mouse Cells Back into Stem Cells

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Abstract

A total of 2131 different expression genes were identified as candidate pluripotency-associated genes in mouse cells.

Global transcriptional profiles of mouse induced pluripotent stem cells (miPSCs) and mouse embryonic stem cells (mESCs) were analyzed from seven different labs, leading to successful clustering by cell type.
There is significant overlap between the differentially expressed genes identified in comparisons of mESCs/miPSCs with somatic cells and between miPSCs and mESCs.
The overlap included 313 miPSC-specific genes expressed at higher levels in miPSCs and 184 mESC-specific genes.
Eighty-six percent of miPSC-specific genes are more highly expressed in somatic cells, while 73% of mESC-specific genes are highly expressed in mESCs/miPSCs.
A strong correlation was found between oocyte-enriched factors and insufficiently induced mESC-specific genes.
Network analysis identified 11 hub genes that may drive reprogramming processes.

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Factor-based induced reprogramming approaches have tremendous potential for human regenerative medicine, but the efficiencies of these approaches are still low. In this study, we analyzed the global transcriptional profiles of mouse induced pluripotent stem cells (miPSCs) and mouse embryonic stem cells (mESCs) from seven different labs and present here the first successful clustering according to cell type, not by lab of origin. We identified 2131 different expression genes (DEs) as candidate pluripotency-associated genes by comparing mESCs/miPSCs with somatic cells and 720 DEs between miPSCs and mESCs. Interestingly, there was a significant overlap between the two DE sets. Therefore, we defined the overlap DEs as "consensus DEs" including 313 miPSC-specific genes expressed at a higher level in miPSCs versus mESCs and 184 mESC-specific genes in total and reasoned that these may contribute to the differences in pluripotency between mESCs and miPSCs. A classification of "consensus DEs" according to their different expression levels between somatic cells and mESCs/miPSCs shows that 86% of the miPSC-specific genes are more highly expressed in somatic cells, while 73% of mESC-specific genes are highly expressed in mESCs/miPSCs, indicating that the miPSCs have not efficiently silenced the expression pattern of the somatic cells from which they are derived and failed to completely induce the genes with high expression levels in mESCs. We further revealed a strong correlation between oocyte-enriched factors and insufficiently induced mESC-specific genes and identified 11 hub genes via network analysis. In light of these findings, we postulated that these key hub genes might not only drive somatic cell nuclear transfer (SCNT) reprogramming but also augment the efficiency and quality of miPSC reprogramming.

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Identifying Candidate Reprogramming Genes in Mouse Induced Pluripotent Stem Cells

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