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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Boisvert EM,Engle SJ,Hallowell SE,Liu P,Wang ZW,Li XJ

doi

10.1038/srep16821

subject

Has Abstract

pub_date

2015-11-19 00:00:00

pages

16821

issn

2045-2322

pii

srep16821

journal_volume

5

pub_type

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