Cyclosporine A-Mediated IL-6 Expression Promotes Neural Induction in Pluripotent Stem Cells

Ashwathnarayan Ashwini, Sushma S. Naganur, Bhaskar Smitha, Preethi Sheshadri, Jyothi Prasanna, Anujith Kumar

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs. We found CsA to increase the expression of neural progenitor genes during early neural differentiation. Gene silencing approach revealed CsA-mediated neural induction to be dependent on blocking the Ca2+-activated phosphatase calcineurin (Cn) signaling. Similar observation with FK506, an independent inhibitor of Cn, further strengthened the necessity of blocking Cn for enhanced neurogenesis. Surprisingly, mechanistic insight revealed Cn-inhibition dependent upregulation of IL-6 protein to be necessary for CsA-mediated neurogenesis. Together, these findings provide a comprehensive understanding of the role of CsA in neurogenesis, thus suggesting a method for obtaining large numbers of neural progenitors from PSCs for possible transplantation.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalMolecular Neurobiology
DOIs
Publication statusPublished - 01-05-2018

Fingerprint

Pluripotent Stem Cells
Neurogenesis
Cyclosporine
Interleukin-6
Calcineurin
Regenerative Medicine
Stem Cell Transplantation
Gene Silencing
Tacrolimus
Immunosuppressive Agents
Up-Regulation
Observation
Research
Pharmaceutical Preparations
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Ashwini, Ashwathnarayan ; Naganur, Sushma S. ; Smitha, Bhaskar ; Sheshadri, Preethi ; Prasanna, Jyothi ; Kumar, Anujith. / Cyclosporine A-Mediated IL-6 Expression Promotes Neural Induction in Pluripotent Stem Cells. In: Molecular Neurobiology. 2018 ; pp. 1-13.
@article{106cb34406e04fdeab61dc6dfeca40b6,
title = "Cyclosporine A-Mediated IL-6 Expression Promotes Neural Induction in Pluripotent Stem Cells",
abstract = "Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs. We found CsA to increase the expression of neural progenitor genes during early neural differentiation. Gene silencing approach revealed CsA-mediated neural induction to be dependent on blocking the Ca2+-activated phosphatase calcineurin (Cn) signaling. Similar observation with FK506, an independent inhibitor of Cn, further strengthened the necessity of blocking Cn for enhanced neurogenesis. Surprisingly, mechanistic insight revealed Cn-inhibition dependent upregulation of IL-6 protein to be necessary for CsA-mediated neurogenesis. Together, these findings provide a comprehensive understanding of the role of CsA in neurogenesis, thus suggesting a method for obtaining large numbers of neural progenitors from PSCs for possible transplantation.",
author = "Ashwathnarayan Ashwini and Naganur, {Sushma S.} and Bhaskar Smitha and Preethi Sheshadri and Jyothi Prasanna and Anujith Kumar",
year = "2018",
month = "5",
day = "1",
doi = "10.1007/s12035-017-0633-0",
language = "English",
pages = "1--13",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",

}

Cyclosporine A-Mediated IL-6 Expression Promotes Neural Induction in Pluripotent Stem Cells. / Ashwini, Ashwathnarayan; Naganur, Sushma S.; Smitha, Bhaskar; Sheshadri, Preethi; Prasanna, Jyothi; Kumar, Anujith.

In: Molecular Neurobiology, 01.05.2018, p. 1-13.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cyclosporine A-Mediated IL-6 Expression Promotes Neural Induction in Pluripotent Stem Cells

AU - Ashwini, Ashwathnarayan

AU - Naganur, Sushma S.

AU - Smitha, Bhaskar

AU - Sheshadri, Preethi

AU - Prasanna, Jyothi

AU - Kumar, Anujith

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs. We found CsA to increase the expression of neural progenitor genes during early neural differentiation. Gene silencing approach revealed CsA-mediated neural induction to be dependent on blocking the Ca2+-activated phosphatase calcineurin (Cn) signaling. Similar observation with FK506, an independent inhibitor of Cn, further strengthened the necessity of blocking Cn for enhanced neurogenesis. Surprisingly, mechanistic insight revealed Cn-inhibition dependent upregulation of IL-6 protein to be necessary for CsA-mediated neurogenesis. Together, these findings provide a comprehensive understanding of the role of CsA in neurogenesis, thus suggesting a method for obtaining large numbers of neural progenitors from PSCs for possible transplantation.

AB - Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs. We found CsA to increase the expression of neural progenitor genes during early neural differentiation. Gene silencing approach revealed CsA-mediated neural induction to be dependent on blocking the Ca2+-activated phosphatase calcineurin (Cn) signaling. Similar observation with FK506, an independent inhibitor of Cn, further strengthened the necessity of blocking Cn for enhanced neurogenesis. Surprisingly, mechanistic insight revealed Cn-inhibition dependent upregulation of IL-6 protein to be necessary for CsA-mediated neurogenesis. Together, these findings provide a comprehensive understanding of the role of CsA in neurogenesis, thus suggesting a method for obtaining large numbers of neural progenitors from PSCs for possible transplantation.

UR - http://www.scopus.com/inward/record.url?scp=85020547248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020547248&partnerID=8YFLogxK

U2 - 10.1007/s12035-017-0633-0

DO - 10.1007/s12035-017-0633-0

M3 - Article

AN - SCOPUS:85020547248

SP - 1

EP - 13

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

ER -