Interleukin-6-Mediated Induced Pluripotent Stem Cell (iPSC)-Derived Neural Differentiation

  • Yanuar Alan Sulistio
  • Han Kyu Lee
  • Sung Jun Jung
  • Klaus Heese
Article

Abstract

In an aging society with an increasing threat to higher brain cognitive functions due to dementia, it becomes imperative to identify new molecular remedies for supporting adult neurogenesis. Interleukin-6 (IL-6) is a promising cytokine that can support neurogenesis under conditions of neurodegeneration, and neuron replacement is eventually possible due to its agonistic acting soluble receptor sIL-6R. Here, we report that activation of the IL-6–signal transducer and activator of transcription 3 (STAT3) axis is neurogenic and has potential therapeutic applications for the treatment of neurodegenerative diseases such as Parkinson’s disease (PD).

Keywords

BDNF Brain Interleukin-6 Neuron Neurotrophin STAT3 

Abbreviations

AD

Alzheimer’s disease

AKT

AKT (mouse Ak strain thymoma) serine/threonine kinase, protein kinase B (PKB)

ALP

Alkaline phosphatase

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AP

Action potential

APC

Allophycocyanin

BDNF

Brain-derived neurotrophic factor

bFGF

Basic fibroblast growth factor

BMP

Bone morphogenetic protein

BSA

Bovine serum albumin

CD15

Cluster of differentiation 15, 3-fucosyl-N-acetyl-lactosamine, SSEA-1 (stage-specific embryonic antigen 1)

CD24

Cluster of differentiation 24 or heat-stable antigen CD24 (HSA)

CD44

Cluster of differentiation 44, HCAM (homing cell adhesion molecule), Pgp-1 (phagocytic glycoprotein-1)

CD184

Cluster of differentiation 184, C-X-C chemokine receptor type 4 (CXCR-4)

CD271

Cluster of differentiation 271, LNGFR (low-affinity nerve growth factor receptor) or p75NTR (neurotrophin receptor p75)

CH3

Methyl-, methylation

CNS

Central nervous system

CNTF

Ciliary neurotrophic factor

CREB

cAMP-responsive element binding protein

Cy

Cyanine

DAPI

4′,6-Diamidino-2-phenylindole

DMEM

Dulbecco’s modified Eagle medium

EDTA

Ethylenediaminetetraacetic acid

EGF

Epidermal growth factor

ERK

Extracellular-regulated microtubule-associated protein kinase

FACS

Fluorescence-activated cell sorting

FBS

Fetal bovine serum

FITC

Fluorescein isothiocyanate

FM

Fibroblast media

FOS

Finkel-Biskis-Jinkins (FBJ) osteosarcoma (Fos) proto-oncogene, activator protein 1 (AP-1) transcription factor subunit

GAB1

GRB2-associated-binding protein 1

GABA

Gamma-aminobutyric acid

GABAA-R

Gamma-aminobutyric acid-A receptor

GF

Growth factor

GFAP

Glial fibrillary acidic protein

i-Glu-R

Ionotropic glutamate receptor

gp130

Glycoprotein 130

GRB2

Growth factor receptor bound protein 2

HEPES

4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid

ICC

Immunocytochemistry

IL-6

Interleukin-6

IL-6R

Interleukin-6 receptor

IL6ST

Interleukin-6 signal transducing receptor subunit (gp130)

iPSCs

Induced pluripotent stem cells

JAK

Janus kinase

JNK

c-Jun N-terminal kinase

JUN

Jun proto-oncogene, activator protein 1 (AP-1) transcription factor subunit

Klf4

Kruppel-like factor 4

Lif

Leukemia inhibitory factor

Lin28

Lin-28 homolog

L-Myc

v-Myc avian myelocytomatosis viral oncogene lung carcinoma-derived homolog

MAP2

Microtubule-associated protein 2

MAPK

Microtubule-associated protein kinase

MAPT

Microtubule-associated protein tau

MKI67

Marker of proliferation Ki-67

MYC

Myelocytomatosis viral oncogene

NB

Neurobasal media

NEUN

Neuronal nuclei, RNA binding protein fox-1 homolog 3 (RBFOX3)

NEAA

Non-essential amino acids

NHDF

Normal human dermal fibroblast cells

NMDA

N-Methyl-d-aspartate

NSC

Neural stem cell

OCT4

POU class 5 homeobox 1 (POU5F1)

P

Passages

p53

Tumor protein 53

PBS

Phosphate buffer saline

PD

Parkinson’s disease

PE

Phycoerythrin cyanine

PerCP

Peridinin chlorophyll protein complex

PFA

Paraformaldehyde

PI3K

Phosphatidylinositol 3-kinase, and phosphatidylinositol-4,5-bisphosphate 3-kinase

PODXL

Podocalyxin-like proteins, also known as TRA-1-60 and TRA-1-81 antigens

P/S

Penicillin, streptomycin

RAS

Sarcoma virus oncogene (small G-protein)

RMP

Resting membrane potential

SFK

src-family kinase

sgp130

Soluble glycoprotein 130

SHP1/2

Protein tyrosine phosphatase, non-receptor type 6, -11 (Ptpn6/11)

shRNA

Short hairpin RNA

sIL-6R

Soluble interleukin-6 receptor

SMAD

Portmanteau of Sma (small) and Mad (mothers against decapentaplegic homolog)

SOCS3

Suppressor of cytokine signaling 3

SOX2/6

Sex-determining region Y (SRY)-box 2, -6

SOS

Son of sevenless protein

SSEA3/4

Stage-specific embryonic antigen 3, -4

STAT3

Signal transducer and activator of transcription 3

TF

Transcription factor

TGFβ

Transforming growth factor beta

TRA-1-60/81

Podocalyxin-like proteins (PODXL, TRA-1-60, and TRA-1-81 antigens)

TRKB

Tropomyosin receptor kinase B, neurotrophic receptor tyrosine kinase 2 (NTRK2)

TRKB.T1

Truncated TRKB (without kinase domain)

TTX

Tetrodotoxin

TUBB3

β-Tubulin isotype III (also TUJ1)

VD

Vascular dementia

YAP

Yes-associated protein

Y-P

Phosphorylated tyrosine

Supplementary material

12035_2017_594_MOESM1_ESM.pdf (3.1 mb)
ESM 1(PDF 3134 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Graduate School of Biomedical Science and EngineeringHanyang UniversitySeongdong-guRepublic of Korea

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