Human peptidergic nociceptive sensory neurons generated from human epidermal neural crest stem cells (hEPI-NCSC)
Here we provide new technology for generating human peptidergic nociceptive sensory neurons in a straightforward and efficient way. The cellular source, human epidermal neural crest stem cells (hEPI-NCSC), consists of multipotent somatic stem cells that reside in the bulge of hair follicles. hEPI-NC...
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Published in | PloS one Vol. 13; no. 6; p. e0199996 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Public Library of Science
28.06.2018
Public Library of Science (PLoS) |
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Abstract | Here we provide new technology for generating human peptidergic nociceptive sensory neurons in a straightforward and efficient way. The cellular source, human epidermal neural crest stem cells (hEPI-NCSC), consists of multipotent somatic stem cells that reside in the bulge of hair follicles. hEPI-NCSC and primary sensory neurons have a common origin, the embryonic neural crest. For directed differentiation, hEPI-NCSC were exposed to pertinent growth factors and small molecules in order to modulate master signalling networks involved in differentiation of neural crest cells into postmitotic peptidergic sensory neurons during embryonic development. The neuronal populations were homogenous in regard to antibody marker expression. Cells were immunoreactive for essential master regulatory genes, including NGN1/2, SOX10, and BRN3a among others, and for the pain-mediating genes substance P (SP), calcitonin gene related protein (CGRP) and the TRPV1 channel. Approximately 30% of total cells responded to capsaicin, indicating that they expressed an active TRPV1 channel. In summary, hEPI-NCSC are a biologically relevant and easily available source of somatic stem cells for generating human peptidergic nociceptive neurons without the need for genetic manipulation and cell purification. As no analgesics exist that specifically target TRPV1, a ready supply of high-quality human peptidergic nociceptive sensory neurons could open the way for new approaches, in a biologically relevant cellular context, to drug discovery and patient-specific disease modelling that is aimed at pain control, and as such is highly desirable. |
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AbstractList | Here we provide new technology for generating human peptidergic nociceptive sensory neurons in a straightforward and efficient way. The cellular source, human epidermal neural crest stem cells (hEPI-NCSC), consists of multipotent somatic stem cells that reside in the bulge of hair follicles. hEPI-NCSC and primary sensory neurons have a common origin, the embryonic neural crest. For directed differentiation, hEPI-NCSC were exposed to pertinent growth factors and small molecules in order to modulate master signalling networks involved in differentiation of neural crest cells into postmitotic peptidergic sensory neurons during embryonic development. The neuronal populations were homogenous in regard to antibody marker expression. Cells were immunoreactive for essential master regulatory genes, including NGN1/2, SOX10, and BRN3a among others, and for the pain-mediating genes substance P (SP), calcitonin gene related protein (CGRP) and the TRPV1 channel. Approximately 30% of total cells responded to capsaicin, indicating that they expressed an active TRPV1 channel. In summary, hEPI-NCSC are a biologically relevant and easily available source of somatic stem cells for generating human peptidergic nociceptive neurons without the need for genetic manipulation and cell purification. As no analgesics exist that specifically target TRPV1, a ready supply of high-quality human peptidergic nociceptive sensory neurons could open the way for new approaches, in a biologically relevant cellular context, to drug discovery and patient-specific disease modelling that is aimed at pain control, and as such is highly desirable. |
Audience | Academic |
Author | Poll, Alistair Ahmmed, Afsara A Laude, Alex Sieber-Blum, Maya Sakaue, Motoharu Wilson, Rachel |
AuthorAffiliation | 2 School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom 1 Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom University of Colorado Boulder, UNITED STATES 3 The Bio-Imaging Unit, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom |
AuthorAffiliation_xml | – name: 2 School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom – name: 3 The Bio-Imaging Unit, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom – name: University of Colorado Boulder, UNITED STATES – name: 1 Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom |
Author_xml | – sequence: 1 givenname: Rachel surname: Wilson fullname: Wilson, Rachel organization: Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom – sequence: 2 givenname: Afsara A surname: Ahmmed fullname: Ahmmed, Afsara A organization: Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom – sequence: 3 givenname: Alistair surname: Poll fullname: Poll, Alistair organization: School of Biology, Newcastle University, Newcastle upon Tyne, United Kingdom – sequence: 4 givenname: Motoharu surname: Sakaue fullname: Sakaue, Motoharu organization: Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom – sequence: 5 givenname: Alex surname: Laude fullname: Laude, Alex organization: The Bio-Imaging Unit, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom – sequence: 6 givenname: Maya orcidid: 0000-0003-0453-300X surname: Sieber-Blum fullname: Sieber-Blum, Maya organization: Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom |
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Copyright | COPYRIGHT 2018 Public Library of Science 2018 Wilson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2018 Wilson et al 2018 Wilson et al |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist. Current address: Department of Veterinary Medicine, Laboratory of Anatomy II, School of Veterinary Medicine, Azabu University, Chuo-ku, Sagamihara, Japan |
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Snippet | Here we provide new technology for generating human peptidergic nociceptive sensory neurons in a straightforward and efficient way. The cellular source, human... |
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SubjectTerms | Analgesics Arthritis Biology and Life Sciences Brn-3 protein Calcitonin Calcitonin gene-related peptide Capsaicin Capsaicin receptors Cell Differentiation Developmental biology Diabetes Diabetic neuropathy Differentiation Disease Disease control Drug discovery Embryogenesis Embryonic growth stage Fibroblasts Follicles Gene expression Gene Expression Regulation Genes Growth factors Humans Molecular chains Multipotent Stem Cells - cytology Multipotent Stem Cells - metabolism Neural crest Neural Crest - cytology Neural Crest - metabolism Neurogenesis Neurons Neuropeptides New technology Nociception Nociceptors - cytology Nociceptors - metabolism Pain Pain perception Physiological aspects Proteins Research and Analysis Methods Sensory neurons Sensory properties Sensory receptors Signal Transduction Sox10 protein Stem cell research Stem cells Substance P Veterinary medicine |
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Title | Human peptidergic nociceptive sensory neurons generated from human epidermal neural crest stem cells (hEPI-NCSC) |
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