Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.
The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.
Pfizer Neusentis, Cambridge, UK. Electronic address: Gareth.Young@pfizer.com.
Gareth T
GT
Young
Pfizer Neusentis, Cambridge, UK.
Alex
A
Gutteridge
Pfizer Neusentis, Cambridge, UK; Current address: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Heather DE
H
Fox
Pfizer Neusentis, Cambridge, UK.
Anna L
AL
Wilbrey
Pfizer Neusentis, Cambridge, UK.
Lishuang
L
Cao
Pfizer Neusentis, Cambridge, UK.
Lily T
LT
Cho
Pfizer Neusentis, Cambridge, UK.
Adam R
AR
Brown
Pfizer Neusentis, Cambridge, UK.
Caroline L
CL
Benn
Pfizer Neusentis, Cambridge, UK.
Laura R
LR
Kammonen
Oncology Research Unit, Pfizer Global Research and Development, Pearl River, NY, USA.
Julia H
JH
Friedman
Pfizer Neusentis, Cambridge, UK.
Magda
M
Bictash
Pfizer Neusentis, Cambridge, UK.
Paul
P
Whiting
Pfizer Neusentis, Cambridge, UK.
James G
JG
Bilsland
Pfizer Neusentis, Cambridge, UK.
Edward B
EB
Stevens
D000814:Aniline Compounds / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D010146:Pain / Q000503:physiopathology; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000502:physiology*; D059010:Single-Cell Analysis
C520740:A 803467; D000814:Aniline Compounds; D005663:Furans; D007473:Ion Channels; D005576:Colforsin