Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors

Stuart M. Chambers, Yuchen Qi, Yvonne Mica, Gabsang Lee, Xin Jun Zhang, Lei Niu, James Bilsland, Lishuang Cao, Edward Stevens, Paul Whiting, Song Hai Shi, Lorenz Studer

Research output: Contribution to journalArticle

Abstract

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, 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.

Original languageEnglish (US)
Pages (from-to)715-720
Number of pages6
JournalNature Biotechnology
Volume30
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

Fingerprint

Pluripotent Stem Cells
Nociceptors
Stem cells
Neurons
Molecules
Capsaicin
Adenosinetriphosphate
Tetrodotoxin
Efficiency
Adenosine Triphosphate
Sodium
Human Development
Inhibition (Psychology)
Pain

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

Cite this

Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. / Chambers, Stuart M.; Qi, Yuchen; Mica, Yvonne; Lee, Gabsang; Zhang, Xin Jun; Niu, Lei; Bilsland, James; Cao, Lishuang; Stevens, Edward; Whiting, Paul; Shi, Song Hai; Studer, Lorenz.

In: Nature Biotechnology, Vol. 30, No. 7, 07.2012, p. 715-720.

Research output: Contribution to journalArticle

Chambers, SM, Qi, Y, Mica, Y, Lee, G, Zhang, XJ, Niu, L, Bilsland, J, Cao, L, Stevens, E, Whiting, P, Shi, SH & Studer, L 2012, 'Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors', Nature Biotechnology, vol. 30, no. 7, pp. 715-720. https://doi.org/10.1038/nbt.2249
Chambers, Stuart M. ; Qi, Yuchen ; Mica, Yvonne ; Lee, Gabsang ; Zhang, Xin Jun ; Niu, Lei ; Bilsland, James ; Cao, Lishuang ; Stevens, Edward ; Whiting, Paul ; Shi, Song Hai ; Studer, Lorenz. / Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors. In: Nature Biotechnology. 2012 ; Vol. 30, No. 7. pp. 715-720.
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