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

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Book cover MicroRNA Protocols

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1733))

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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Authors and Affiliations

  1. Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Shao-Yao Ying & William Fang

  2. Division of Regenerative Medicine, WJWU & LYNN (W&L) Institute for Stem Cell Research, Santa Fe Springs, CA, USA

    Shi-Lung Lin

Authors
  1. Shao-Yao Ying
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  2. William Fang
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  3. Shi-Lung Lin
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Corresponding author

Correspondence to Shao-Yao Ying .

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Editors and Affiliations

  1. Department of Integrative Anatomical Sciences, USC, Keck School of Medicine, Los Angeles, California, USA

    Shao-Yao Ying

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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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  • DOI: https://doi.org/10.1007/978-1-4939-7601-0_23

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7600-3

  • Online ISBN: 978-1-4939-7601-0

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