Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization
Somatosensation, the detection and transduction of external and internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some of the mechanisms of distinct stimuli detection and transduction are not entirely understood, especially when noxious...
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MDPI AG
2022-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/18/2905 |
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| author | Katrin Schrenk-Siemens Jörg Pohle Charlotte Rostock Muad Abd El Hay Ruby M. Lam Marcin Szczot Shiying Lu Alexander T. Chesler Jan Siemens |
| author_facet | Katrin Schrenk-Siemens Jörg Pohle Charlotte Rostock Muad Abd El Hay Ruby M. Lam Marcin Szczot Shiying Lu Alexander T. Chesler Jan Siemens |
| author_sort | Katrin Schrenk-Siemens |
| collection | DOAJ |
| description | Somatosensation, the detection and transduction of external and internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some of the mechanisms of distinct stimuli detection and transduction are not entirely understood, especially when noxious perception turns into chronic pain. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. However, it is in particular the access to human pluripotent stem cells and the possibility of generating and studying human sensory neurons that has enriched the somatosensory research field. Based on our previous work, we describe here the generation of human stem cell-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations with different responsiveness to nociceptive stimuli such as capsaicin. Functional as well as deep sequencing analysis demonstrated that one protocol in particular allowed the generation of a mechano-nociceptive sensory neuron population, homogeneously expressing TRPV1. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation. The efficient and homogenous generation of these neurons make them an ideal translational tool to study mechanisms of sensitization, also in the context of chronic pain. |
| first_indexed | 2024-03-10T00:25:30Z |
| format | Article |
| id | doaj.art-32b7e61ed6dc41b6981cbf3ecae367cb |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:25:30Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-32b7e61ed6dc41b6981cbf3ecae367cb2023-11-23T15:34:13ZengMDPI AGCells2073-44092022-09-011118290510.3390/cells11182905Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of SensitizationKatrin Schrenk-Siemens0Jörg Pohle1Charlotte Rostock2Muad Abd El Hay3Ruby M. Lam4Marcin Szczot5Shiying Lu6Alexander T. Chesler7Jan Siemens8Department of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, GermanyNational Center for Complementary and Integrative Health, NIH, 35A Convent Drive, Bethesda, MD 20892, USANational Center for Complementary and Integrative Health, NIH, 35A Convent Drive, Bethesda, MD 20892, USADepartment of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, GermanyNational Center for Complementary and Integrative Health, NIH, 35A Convent Drive, Bethesda, MD 20892, USADepartment of Pharmacology, Im Neuenheimer Feld 366, University of Heidelberg, 69120 Heidelberg, GermanySomatosensation, the detection and transduction of external and internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some of the mechanisms of distinct stimuli detection and transduction are not entirely understood, especially when noxious perception turns into chronic pain. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. However, it is in particular the access to human pluripotent stem cells and the possibility of generating and studying human sensory neurons that has enriched the somatosensory research field. Based on our previous work, we describe here the generation of human stem cell-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations with different responsiveness to nociceptive stimuli such as capsaicin. Functional as well as deep sequencing analysis demonstrated that one protocol in particular allowed the generation of a mechano-nociceptive sensory neuron population, homogeneously expressing TRPV1. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation. The efficient and homogenous generation of these neurons make them an ideal translational tool to study mechanisms of sensitization, also in the context of chronic pain.https://www.mdpi.com/2073-4409/11/18/2905somatosensationhuman pluripotent stem cellsnociceptor-like cellshomogenous neuronal populationTRPV1 responderstranslational tool |
| spellingShingle | Katrin Schrenk-Siemens Jörg Pohle Charlotte Rostock Muad Abd El Hay Ruby M. Lam Marcin Szczot Shiying Lu Alexander T. Chesler Jan Siemens Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization Cells somatosensation human pluripotent stem cells nociceptor-like cells homogenous neuronal population TRPV1 responders translational tool |
| title | Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization |
| title_full | Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization |
| title_fullStr | Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization |
| title_full_unstemmed | Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization |
| title_short | Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization |
| title_sort | human stem cell derived trpv1 positive sensory neurons a new tool to study mechanisms of sensitization |
| topic | somatosensation human pluripotent stem cells nociceptor-like cells homogenous neuronal population TRPV1 responders translational tool |
| url | https://www.mdpi.com/2073-4409/11/18/2905 |
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