Identification of potential transcription factors that enhance human iPSC generation

Abstract

Although many factors have been identified and used to enhance the iPSC reprogramming process, its efficiency remains quite low. In addition, reprogramming efficacy has been evidenced to be affected by disease mutations that are present in patient samples. In this study, using RNA-seq platform we have identified and validated the differential gene expression of five transcription factors (TFs) (GBX2, NANOGP8, SP8, PEG3, and ZIC1) that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson's disease. We have applied different bioinformatics tools (Gene ontology, protein–protein interaction, and signaling pathways analyses) to investigate the possible roles of these TFs in pluripotency and developmental process. Interestingly, GBX2, NANOGP8, SP8, PEG3, and ZIC1 were found to play a role in maintaining pluripotency, regulating self-renewal stages, and interacting with other factors that are involved in pluripotency regulation including OCT4, SOX2, NANOG, and KLF4. Therefore, the TFs identified in this study could be used as additional transcription factors that enhance reprogramming efficiency to boost iPSC generation technology. The concept of somatic cell reprogramming is based on the presence of a combination of factors and conditions to generate induced pluripotent stem cells (iPSCs)1. Several factors have been found to play a crucial role in reprogramming since the discovery of iPSCs of which the ectopic expression of OCT3/4, SOX2, KLF4, and c-MYC (OSKM) is known to be the most robust method2,3,4. Although the process of somatic cell reprogramming into a pluripotent state simply depends on ectopic expression of pluripotent genes, it remains inefficient and only a small number of cells can undergo complete reprogramming.

Keywords Disease mutations, Generation technology, Patient samples ,Gene ontology