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


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).

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Alzheimer’s disease


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


Alkaline phosphatase


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


Action potential




Brain-derived neurotrophic factor


Basic fibroblast growth factor


Bone morphogenetic protein


Bovine serum albumin


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


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


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


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


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


Methyl-, methylation


Central nervous system


Ciliary neurotrophic factor


cAMP-responsive element binding protein






Dulbecco’s modified Eagle medium


Ethylenediaminetetraacetic acid


Epidermal growth factor


Extracellular-regulated microtubule-associated protein kinase


Fluorescence-activated cell sorting


Fetal bovine serum


Fluorescein isothiocyanate


Fibroblast media


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


GRB2-associated-binding protein 1


Gamma-aminobutyric acid


Gamma-aminobutyric acid-A receptor


Growth factor


Glial fibrillary acidic protein


Ionotropic glutamate receptor


Glycoprotein 130


Growth factor receptor bound protein 2


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






Interleukin-6 receptor


Interleukin-6 signal transducing receptor subunit (gp130)


Induced pluripotent stem cells


Janus kinase


c-Jun N-terminal kinase


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


Kruppel-like factor 4


Leukemia inhibitory factor


Lin-28 homolog


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


Microtubule-associated protein 2


Microtubule-associated protein kinase


Microtubule-associated protein tau


Marker of proliferation Ki-67


Myelocytomatosis viral oncogene


Neurobasal media


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


Non-essential amino acids


Normal human dermal fibroblast cells




Neural stem cell


POU class 5 homeobox 1 (POU5F1)




Tumor protein 53


Phosphate buffer saline


Parkinson’s disease


Phycoerythrin cyanine


Peridinin chlorophyll protein complex




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


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


Penicillin, streptomycin


Sarcoma virus oncogene (small G-protein)


Resting membrane potential


src-family kinase


Soluble glycoprotein 130


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


Short hairpin RNA


Soluble interleukin-6 receptor


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


Suppressor of cytokine signaling 3


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


Son of sevenless protein


Stage-specific embryonic antigen 3, -4


Signal transducer and activator of transcription 3


Transcription factor


Transforming growth factor beta


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


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


Truncated TRKB (without kinase domain)




β-Tubulin isotype III (also TUJ1)


Vascular dementia


Yes-associated protein


Phosphorylated tyrosine


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This study was supported by Hanyang University by providing a scholarship to Y.A.S. and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2009178).

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Correspondence to Klaus Heese.

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Sulistio, Y.A., Lee, H.K., Jung, S.J. et al. Interleukin-6-Mediated Induced Pluripotent Stem Cell (iPSC)-Derived Neural Differentiation. Mol Neurobiol 55, 3513–3522 (2018).

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  • BDNF
  • Brain
  • Interleukin-6
  • Neuron
  • Neurotrophin
  • STAT3