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HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction

Katrin Schrenk-Siemens, Jörg Pohle, Charlotte Rostock, Muad Abd El Hay, Ruby M. Lam, Marcin Szczot, Shiying Lu, Alexander T. Chesler, Jan Siemens
doi: https://doi.org/10.1101/741660
Katrin Schrenk-Siemens
1Department of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany
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  • For correspondence: jan.siemens@pharma.uni-heidelberg.de katrin.schrenk-siemens@pharma.uni-heidelberg.de
Jörg Pohle
1Department of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany
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Charlotte Rostock
1Department of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany
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Muad Abd El Hay
1Department of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany
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Ruby M. Lam
2National Center for Complementary and Integrative Health, NIH, 35A Convent Drive, Bethesda, MD 20892, USA
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Marcin Szczot
2National Center for Complementary and Integrative Health, NIH, 35A Convent Drive, Bethesda, MD 20892, USA
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Shiying Lu
1Department of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany
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Alexander T. Chesler
2National Center for Complementary and Integrative Health, NIH, 35A Convent Drive, Bethesda, MD 20892, USA
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Jan Siemens
1Department of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, Germany
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  • For correspondence: jan.siemens@pharma.uni-heidelberg.de katrin.schrenk-siemens@pharma.uni-heidelberg.de
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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.

Based 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.

Surprisingly, all of the generated subtypes show mechano-nociceptive characteristics and, quite unexpectedly, loss of mechanotransduction in the absence of PIEZO2.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 23, 2019.
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HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction
Katrin Schrenk-Siemens, Jörg Pohle, Charlotte Rostock, Muad Abd El Hay, Ruby M. Lam, Marcin Szczot, Shiying Lu, Alexander T. Chesler, Jan Siemens
bioRxiv 741660; doi: https://doi.org/10.1101/741660
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HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction
Katrin Schrenk-Siemens, Jörg Pohle, Charlotte Rostock, Muad Abd El Hay, Ruby M. Lam, Marcin Szczot, Shiying Lu, Alexander T. Chesler, Jan Siemens
bioRxiv 741660; doi: https://doi.org/10.1101/741660

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