HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction
Siemens, J.; Schrenk-Siemens, K.; Pohle, J.; Rostock, C.; Abd El Hay, M.; Lam, R. M.; Szczot, M.; Lu, S.; Chesler, A.
Show abstract
Somatosensation, the detection and transduction of external and internal stimuli, has fascinated scientists for centuries. But still, some of the mechanisms how distinct stimuli are detected and transduced are not entirely understood. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. Additionally, the accessibility to human pluripotent stem cells and the possibility to generate and study human sensory neurons has enriched the somatosensory research field.\n\nBased on our previous work, the generation of functional human mechanoreceptors, we describe here the generation of hESC-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations. One protocol in particular allowed the generation of a sensory neuron population, homogeneously expressing TRPV1, a prototypical marker for nociceptors. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation.\n\nSurprisingly, all of the generated subtypes show mechano-nociceptive characteristics and, quite unexpectedly, loss of mechanotransduction in the absence of PIEZO2.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes 96%
- Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons 95%
- Olfactory ensheathing cells from adult female rats are hybrid glia that promote neural repair 94%
Similar papers in this journal
- A human in vitro neuronal model for studying homeostatic plasticity at the network level 95%
- Single cell transcriptomics reveals correct developmental dynamics and high-quality midbrain cell types by improved hESC differentiation. 94%
- Rostrocaudal Patterning and Neural Crest Differentiation of Human Pre-Neural Spinal Cord Progenitors in vitro 94%
Similar papers in this journal
- ASIC3-dependent spinal cord nociceptive signaling in cutaneous pain induced by lysophosphatidyl-choline 95%
- Neuronal development shapes activity-dependent gene expression in a stimulus-specific manner 94%
- Nano-pulling stimulates axon regeneration in dorsal root ganglia by inducing stabilization of axonal microtubules and activation of local translation 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.