The miR-302-Mediated Induction of Pluripotent Stem Cells (iPSC): Multiple Synergistic Reprogramming Mechanisms

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 1733; p. 283
• Main Authors: Ying, Shao-Yao, Fang, William, Lin, Shi-Lung
• Format: Journal Article
• Language: English
• Published: United States 01.01.2018
• Subjects: Animals; Cell Differentiation - genetics; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cellular Reprogramming - genetics; DNA Methylation; Drug Resistance, Neoplasm; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Genomics - methods; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; MicroRNAs - genetics; Neoplasm Metastasis; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - prevention & control; Signal Transduction; Induced pluripotent stem cell; DNA demethylation; miR-302; MicroRNA; Epigenetic reprogramming; Pluripotency
• ISSN: 1940-6029
• DOI: 10.1007/978-1-4939-7601-0_23

Pluripotency represents a unique feature of embryonic stem cells (ESCs). To generate ESC-like-induced pluripotent stem cells (iPSCs) derived from somatic cells, the cell genome needs to be reset and reprogrammed to express the ESC-specific transcriptome. Numerous studies have shown that genomic DNA demethylation is required for epigenetic reprogramming of somatic cell nuclei to form iPSCs; yet, the mechanism remains largely unclear. In ESCs, the reprogramming process goes through two critical stages: germline and zygotic demethylation, both of which erase genomic DNA methylation sites and hence allow for different gene expression patterns to be reset into a pluripotent state. Recently, miR-302, an ESC-specific microRNA (miRNA), was found to play an essential role in four aspects of this reprogramming mechanism-(1) initiating global genomic DNA demethylation, (2) activating ESC-specific gene expression, (3) inhibiting developmental signaling, and (4) preventing stem cell tumorigenicity. In this review, we will summarize miR-302 functions in all four reprogramming aspects and further discuss how these findings may improve the efficiency and safety of the current iPSC technology.