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 journalArticlepeer-review

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors'. Together they form a unique fingerprint.

Cite this