AI Article Synopsis
- Researchers have made significant advancements in how human pluripotent stem cells (hPSCs) can be transformed into specific cell types like neurons, but traditional methods are slow and mimic natural development timelines.
- A screening of small molecules led to the discovery of a combination that allows for the efficient generation of hPSC-derived neurons (over 75% efficiency) within just 10 days.
- These neurons display characteristics of human nociceptors and form much faster than they would in actual human development, indicating potential new methods for studying pain.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516136 | PMC |
| http://dx.doi.org/10.1038/nbt.2249 | DOI Listing |
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