title: The Specification and Maturation of Nociceptive Neurons from Human Embryonic Stem Cells.
abstract: Nociceptive neurons play an essential role in pain sensation by transmitting painful stimuli to the central nervous system. However, investigations of nociceptive neuron biology have been hampered by the lack of accessibility of human nociceptive neurons. Here, we describe a system for efficiently guiding human embryonic stem cells into nociceptive neurons by first inducing these cells to the neural lineage. Subsequent addition of retinoic acid and BMP4 at specific time points and concentrations yielded a high population of neural crest progenitor cells (AP2α(+), P75(+)), which further differentiated into nociceptive neurons (TRKA(+), Nav1.7(+), P2X3(+)). The overexpression of Neurogenin 1 (Neurog1) promoted the neurons to express genes related to sensory neurons (Peripherin, TrkA) and to further mature into TRPV1(+) nociceptive neurons. Importantly, the overexpression of Neurog1 increased the response of these neurons to capsaicin stimulation, a hallmark of mature functional nociceptive neurons. Taken together, this study reveals the important role that Neurog1 plays in generating functional human nociceptive neurons.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030.|Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Boisvert
authors.affiliation: Pharmacokinetics, Dynamics, Metabolism-New Chemical Entities, Pfizer Worldwide Research and Development, Pfizer Inc., Groton, CT 06340.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Engle
authors.affiliation: Pharmacokinetics, Dynamics, Metabolism-New Chemical Entities, Pfizer Worldwide Research and Development, Pfizer Inc., Groton, CT 06340.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Hallowell
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Zhao-Wen
authors.initials: ZW
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030.|Stem Cell Institute, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000166:cytology; D015222:Sodium Channels / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D014212:Tretinoin; C105389:NEUROG1 protein, human