Abstract
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.
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Abbreviations
- 3′-UTRs:
-
The 3′-untranslated regions
- 5hmC:
-
5-Hysroxymethylcytosine
- Ago 1–4:
-
Argonaute proteins 1–4
- AID:
-
Activation-induced cytidine deaminase
- AOF1/2 (LSD1/2 or KMD1/1B):
-
Flavin-containing amine oxidase domain-containing protein ½
- BER:
-
A base excision DNA repair
- BMI-1:
-
B Lymphoma mouse Moloney leukemia virus insertion region
- BMP:
-
Bone morphogenetic protein
- cMyc:
-
c-Myelocytomatosis oncogene
- CXCR4:
-
C-X-C Chemokine receptor type 4
- DAZAP2:
-
DAZ-associated protein 2
- DNMT1:
-
DNA (Cytosine-5-)-methyltransferase 1
- EIF2C:
-
Eukaryotic translation initiation factor 2C
- ESC:
-
Embryonic stem cells
- GCNF or NR6A1:
-
Germ cell nuclear factor
- H3K4me2/3:
-
Methylation of histone 3 on lysine 4
- HDAC2/4:
-
Histone deacetylase 2 and 4
- HDM2:
-
E3 ubiquitin ligase for p53
- iPSCs:
-
Induced pluripotent stem cells
- Klf4:
-
Kruppel-like factor 4
- LARP7 or PIP7S:
-
La ribonucleoprotein domain family member 7 gene
- LIN28:
-
RNA-binding protein LIN-28
- mdm2:
-
P53 E3 ubiquitin protein ligase
- MEPC1/2:
-
Methyl-CpG binding 1 and 2
- miR-302:
-
MicroRNA-302
- miRNA:
-
MicroRNA
- miRNAs:
-
MicroRNAs
- mirPS cells:
-
miR-302-mediated pluripotent stem cells
- NANOG:
-
A transcription factor critically involved with self-renewal of undifferentiated embryonic stem cells
- ncRNAs:
-
Noncoding RNAs
- NR2F2:
-
Nuclear receptor subfamily 2, group F, member 2
- Oct4:
-
Octamer-binding transcription factor 4; a protein that is critically involved in the self-renewal of undifferentiated embryonic stem cells
- PCAF:
-
p300-CBP-associated factor
- PGC:
-
Primordial germ cells
- pre-miRNA:
-
Hairpin-like miRNA precursors
- pri-miRNA:
-
Primary miRNA precursors
- RAS-MAPK:
-
Ras-mitogen-activated protein kinase
- RISC:
-
RNA-induced silencing complexes
- RNA pol II:
-
Type-II RNA polymerases
- SCNT:
-
Somatic cell nuclear transfer
- SCR:
-
Somatic cell reprogramming
- SLAIN1:
-
SLAIN motif family, member 1
- Sox2:
-
SRY (sex determining region Y)-box 2
- SSEA ¾:
-
3-Mercaptopyruvate sulfurtransferase-3 or 4
- Tcf3:
-
Transcription factor 3
- Tet:
-
Tet methylcytosine dioxygenase 1 or 2
- TGFβ-SMAD:
-
Transforming growth factorβ-mothers against DPP homolog family members
- TOB2:
-
Protein Tob2; transducer of erbB-2 2
- UTF1:
-
Undifferentiated embryonic cell transcription factor 1
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Ying, SY., Fang, W., Lin, SL. (2018). The miR-302-Mediated Induction of Pluripotent Stem Cells (iPSC): Multiple Synergistic Reprogramming Mechanisms. In: Ying, SY. (eds) MicroRNA Protocols . Methods in Molecular Biology, vol 1733. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7601-0_23
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