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Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors
by
Bilsland, James
, Zhang, Xin-Jun
, Chambers, Stuart M
, Stevens, Edward
, Lee, Gabsang
, Cao, Lishuang
, Whiting, Paul
, Shi, Song-Hai
, Qi, Yuchen
, Niu, Lei
, Studer, Lorenz
, Mica, Yvonne
in
631/532/2064
/ 631/61/490
/ 631/61/51/1844/2319
/ 631/92/613
/ Acetanilides - pharmacology
/ Adenosine triphosphatase
/ Agriculture
/ ATP
/ Bioinformatics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Biomedicine
/ Biotechnology
/ Caffeic Acids - pharmacology
/ Cell Culture Techniques
/ Cell Differentiation - drug effects
/ Cell Line
/ Diverse techniques
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Developmental - drug effects
/ Humans
/ Inhibitors
/ letter
/ Life Sciences
/ Molecular and cellular biology
/ Molecular biology
/ Molecular Sequence Data
/ NAV1.8 Voltage-Gated Sodium Channel - metabolism
/ Neurons
/ Nociceptors
/ Nociceptors - cytology
/ Nociceptors - drug effects
/ Nociceptors - metabolism
/ Pain
/ Pain - metabolism
/ Pain - physiopathology
/ Physiological aspects
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - drug effects
/ Pluripotent Stem Cells - metabolism
/ Pyridines - pharmacology
/ Pyrimidines - pharmacology
/ Pyrroles - pharmacology
/ Signal transduction
/ Signal Transduction - drug effects
/ Small Molecule Libraries - chemistry
/ Small Molecule Libraries - pharmacology
/ Sodium
/ Stem cells
/ Tetrodotoxin - pharmacology
2012
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Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors
by
Bilsland, James
, Zhang, Xin-Jun
, Chambers, Stuart M
, Stevens, Edward
, Lee, Gabsang
, Cao, Lishuang
, Whiting, Paul
, Shi, Song-Hai
, Qi, Yuchen
, Niu, Lei
, Studer, Lorenz
, Mica, Yvonne
in
631/532/2064
/ 631/61/490
/ 631/61/51/1844/2319
/ 631/92/613
/ Acetanilides - pharmacology
/ Adenosine triphosphatase
/ Agriculture
/ ATP
/ Bioinformatics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Biomedicine
/ Biotechnology
/ Caffeic Acids - pharmacology
/ Cell Culture Techniques
/ Cell Differentiation - drug effects
/ Cell Line
/ Diverse techniques
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Developmental - drug effects
/ Humans
/ Inhibitors
/ letter
/ Life Sciences
/ Molecular and cellular biology
/ Molecular biology
/ Molecular Sequence Data
/ NAV1.8 Voltage-Gated Sodium Channel - metabolism
/ Neurons
/ Nociceptors
/ Nociceptors - cytology
/ Nociceptors - drug effects
/ Nociceptors - metabolism
/ Pain
/ Pain - metabolism
/ Pain - physiopathology
/ Physiological aspects
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - drug effects
/ Pluripotent Stem Cells - metabolism
/ Pyridines - pharmacology
/ Pyrimidines - pharmacology
/ Pyrroles - pharmacology
/ Signal transduction
/ Signal Transduction - drug effects
/ Small Molecule Libraries - chemistry
/ Small Molecule Libraries - pharmacology
/ Sodium
/ Stem cells
/ Tetrodotoxin - pharmacology
2012
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Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors
by
Bilsland, James
, Zhang, Xin-Jun
, Chambers, Stuart M
, Stevens, Edward
, Lee, Gabsang
, Cao, Lishuang
, Whiting, Paul
, Shi, Song-Hai
, Qi, Yuchen
, Niu, Lei
, Studer, Lorenz
, Mica, Yvonne
in
631/532/2064
/ 631/61/490
/ 631/61/51/1844/2319
/ 631/92/613
/ Acetanilides - pharmacology
/ Adenosine triphosphatase
/ Agriculture
/ ATP
/ Bioinformatics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Biomedicine
/ Biotechnology
/ Caffeic Acids - pharmacology
/ Cell Culture Techniques
/ Cell Differentiation - drug effects
/ Cell Line
/ Diverse techniques
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Developmental - drug effects
/ Humans
/ Inhibitors
/ letter
/ Life Sciences
/ Molecular and cellular biology
/ Molecular biology
/ Molecular Sequence Data
/ NAV1.8 Voltage-Gated Sodium Channel - metabolism
/ Neurons
/ Nociceptors
/ Nociceptors - cytology
/ Nociceptors - drug effects
/ Nociceptors - metabolism
/ Pain
/ Pain - metabolism
/ Pain - physiopathology
/ Physiological aspects
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - drug effects
/ Pluripotent Stem Cells - metabolism
/ Pyridines - pharmacology
/ Pyrimidines - pharmacology
/ Pyrroles - pharmacology
/ Signal transduction
/ Signal Transduction - drug effects
/ Small Molecule Libraries - chemistry
/ Small Molecule Libraries - pharmacology
/ Sodium
/ Stem cells
/ Tetrodotoxin - pharmacology
2012
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Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors
Journal Article
Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors
2012
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Overview
Chambers
et al
. use a combination of small-molecule pathway inhibitors to rapidly differentiate human pluripotent stem cells into nociceptors, a type of sensory neuron. The conversion occurs about three-fold faster than during development, suggesting that pathway inhibition may offer a general approach for speeding up the generation of specific cell types
in vitro
.
Considerable progress has been made in identifying signaling pathways that direct the differentiation of human pluripotent stem cells (hPSCs) into specialized cell types, including neurons. However, differentiation of hPSCs with extrinsic factors is a slow, step-wise process, mimicking the protracted timing of human development. Using a small-molecule screen, we identified a combination of five small-molecule pathway inhibitors that yield hPSC-derived neurons at >75% efficiency within 10 d of differentiation. The resulting neurons express canonical markers and functional properties of human nociceptors, including tetrodotoxin (TTX)-resistant, SCN10A-dependent sodium currents and response to nociceptive stimuli such as ATP and capsaicin. Neuronal fate acquisition occurs about threefold faster than during
in vivo
development
1
, suggesting that use of small-molecule pathway inhibitors could become a general strategy for accelerating developmental timing
in vitro
. The quick and high-efficiency derivation of nociceptors offers unprecedented access to this medically relevant cell type for studies of human pain.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ ATP
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Caffeic Acids - pharmacology
/ Cell Differentiation - drug effects
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Developmental - drug effects
/ Humans
/ letter
/ Molecular and cellular biology
/ NAV1.8 Voltage-Gated Sodium Channel - metabolism
/ Neurons
/ Pain
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - drug effects
/ Pluripotent Stem Cells - metabolism
/ Signal Transduction - drug effects
/ Small Molecule Libraries - chemistry
/ Small Molecule Libraries - pharmacology
/ Sodium
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