STAT3 modulation to enhance motor neuron differentiation in human neural stem cells

Rajalaxmi Natarajan, Vinamrata Singal, Richard Benes, Junling Gao, Hoi Chan, Haijun Chen, Yongjia Yu, Jia Zhou, Ping Wu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2 (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF), which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2)+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases.

Original languageEnglish (US)
Article numbere100405
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 19 2014

Fingerprint

STAT3 Transcription Factor
Neural Stem Cells
Motor Neurons
motor neurons
Stem cells
Neurons
stem cells
transcription (genetics)
Modulation
fibroblast growth factor 2
Fibroblast Growth Factor 2
Niclosamide
niclosamide
neuroglia
Cicatrix
Neurodegenerative diseases
Phosphorylation
homeotic genes
Microtubule-Associated Proteins
Homeobox Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

STAT3 modulation to enhance motor neuron differentiation in human neural stem cells. / Natarajan, Rajalaxmi; Singal, Vinamrata; Benes, Richard; Gao, Junling; Chan, Hoi; Chen, Haijun; Yu, Yongjia; Zhou, Jia; Wu, Ping.

In: PLoS One, Vol. 9, No. 6, e100405, 19.06.2014.

Research output: Contribution to journalArticle

Natarajan R, Singal V, Benes R, Gao J, Chan H, Chen H et al. STAT3 modulation to enhance motor neuron differentiation in human neural stem cells. PLoS One. 2014 Jun 19;9(6). e100405. https://doi.org/10.1371/journal.pone.0100405
Natarajan, Rajalaxmi ; Singal, Vinamrata ; Benes, Richard ; Gao, Junling ; Chan, Hoi ; Chen, Haijun ; Yu, Yongjia ; Zhou, Jia ; Wu, Ping. / STAT3 modulation to enhance motor neuron differentiation in human neural stem cells. In: PLoS One. 2014 ; Vol. 9, No. 6.
@article{2cdf5533a70b4fc094e9432eb9f39392,
title = "STAT3 modulation to enhance motor neuron differentiation in human neural stem cells",
abstract = "Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2 (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF), which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2)+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases.",
author = "Rajalaxmi Natarajan and Vinamrata Singal and Richard Benes and Junling Gao and Hoi Chan and Haijun Chen and Yongjia Yu and Jia Zhou and Ping Wu",
year = "2014",
month = "6",
day = "19",
doi = "10.1371/journal.pone.0100405",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - STAT3 modulation to enhance motor neuron differentiation in human neural stem cells

AU - Natarajan, Rajalaxmi

AU - Singal, Vinamrata

AU - Benes, Richard

AU - Gao, Junling

AU - Chan, Hoi

AU - Chen, Haijun

AU - Yu, Yongjia

AU - Zhou, Jia

AU - Wu, Ping

PY - 2014/6/19

Y1 - 2014/6/19

N2 - Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2 (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF), which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2)+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases.

AB - Spinal cord injury or amyotrophic lateral sclerosis damages spinal motor neurons and forms a glial scar, which prevents neural regeneration. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in astrogliogenesis and scar formation, and thus a fine modulation of STAT3 signaling may help to control the excessive gliogenic environment and enhance neural repair. The objective of this study was to determine the effect of STAT3 inhibition on human neural stem cells (hNSCs). In vitro hNSCs primed with fibroblast growth factor 2 (FGF2) exhibited a lower level of phosphorylated STAT3 than cells primed by epidermal growth factor (EGF), which correlated with a higher number of motor neurons differentiated from FGF2-primed hNSCs. Treatment with STAT3 inhibitors, Stattic and Niclosamide, enhanced motor neuron differentiation only in FGF2-primed hNSCs, as shown by increased homeobox gene Hb9 mRNA levels as well as HB9+ and microtubule-associated protein 2 (MAP2)+ co-labeled cells. The increased motor neuron differentiation was accompanied by a decrease in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes. Interestingly, Stattic and Niclosamide did not affect the level of STAT3 phosphorylation; rather, they perturbed the nuclear translocation of phosphorylated STAT3. In summary, we demonstrate that FGF2 is required for motor neuron differentiation from hNSCs and that inhibition of STAT3 further increases motor neuron differentiation at the expense of astrogliogenesis. Our study thus suggests a potential benefit of targeting the STAT3 pathway for neurotrauma or neurodegenerative diseases.

UR - http://www.scopus.com/inward/record.url?scp=84903382411&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903382411&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0100405

DO - 10.1371/journal.pone.0100405

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e100405

ER -