Scalable generation of sensory neurons from human pluripotent stem cells

Tao Deng; Vukasin M. Jovanovic; Carlos A. Tristan; Claire Weber; Pei Hsuan Chu; Jason Inman; Seungmi Ryu; Yogita Jethmalani; Juliana Ferreira de Sousa; Pinar Ormanoglu; Prisca Twumasi; Chaitali Sen; Jaehoon Shim; Selwyn Jayakar; Han Xiong Bear Zhang; Sooyeon Jo; Weifeng Yu; Ty C. Voss; Anton Simeonov; Bruce P. Bean; Clifford J. Woolf; Ilyas Singeç

doi:10.1016/j.stemcr.2023.03.006

Scalable generation of sensory neurons from human pluripotent stem cells

Tao Deng, Vukasin M. Jovanovic, Carlos A. Tristan, Claire Weber, Pei Hsuan Chu, Jason Inman, Seungmi Ryu, Yogita Jethmalani, Juliana Ferreira de Sousa, Pinar Ormanoglu, Prisca Twumasi, Chaitali Sen, Jaehoon Shim, Selwyn Jayakar, Han Xiong Bear Zhang, Sooyeon Jo, Weifeng Yu, Ty C. Voss, Anton Simeonov, Bruce P. BeanClifford J. Woolf, Ilyas Singeç

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types. Following principles of developmental biology and translational applicability, here we developed an efficient stepwise differentiation method for peptidergic and non-peptidergic nociceptors. By modulating specific cell signaling pathways, hPSCs were first converted into SOX10⁺ neural crest, followed by differentiation into sensory neurons. Detailed characterization, including ultrastructural analysis, confirmed that the hPSC-derived nociceptors displayed cellular and molecular features comparable to native dorsal root ganglion (DRG) neurons, and expressed high-threshold primary sensory neuron markers, transcription factors, neuropeptides, and over 150 ion channels and receptors relevant for pain research and axonal growth/regeneration studies (e.g., TRPV1, NA_V1.7, NA_V1.8, TAC1, CALCA, GAP43, DPYSL2, NMNAT2). Moreover, after confirming robust functional activities and differential response to noxious stimuli and specific drugs, a robotic cell culture system was employed to produce large quantities of human sensory neurons, which can be used to develop nociceptor-selective analgesics.

Original language	English
Pages (from-to)	1030-1047
Number of pages	18
Journal	Stem Cell Reports
Volume	18
Issue number	4
DOIs	https://doi.org/10.1016/j.stemcr.2023.03.006
State	Published - 11 Apr 2023
Externally published	Yes

Keywords

CEPT cocktail
analgesics
cell differentiation
drug testing
iPS cells
neural crest
nociceptor
opioid crisis
pain
sensory neuron

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.stemcr.2023.03.006

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Deng, T., Jovanovic, V. M., Tristan, C. A., Weber, C., Chu, P. H., Inman, J., Ryu, S., Jethmalani, Y., Ferreira de Sousa, J., Ormanoglu, P., Twumasi, P., Sen, C., Shim, J., Jayakar, S., Bear Zhang, H. X., Jo, S., Yu, W., Voss, T. C., Simeonov, A., ... Singeç, I. (2023). Scalable generation of sensory neurons from human pluripotent stem cells. Stem Cell Reports, 18(4), 1030-1047. https://doi.org/10.1016/j.stemcr.2023.03.006

@article{59e095162faf4cf4807b85aa693b0a6f,

title = "Scalable generation of sensory neurons from human pluripotent stem cells",

abstract = "Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types. Following principles of developmental biology and translational applicability, here we developed an efficient stepwise differentiation method for peptidergic and non-peptidergic nociceptors. By modulating specific cell signaling pathways, hPSCs were first converted into SOX10+ neural crest, followed by differentiation into sensory neurons. Detailed characterization, including ultrastructural analysis, confirmed that the hPSC-derived nociceptors displayed cellular and molecular features comparable to native dorsal root ganglion (DRG) neurons, and expressed high-threshold primary sensory neuron markers, transcription factors, neuropeptides, and over 150 ion channels and receptors relevant for pain research and axonal growth/regeneration studies (e.g., TRPV1, NAV1.7, NAV1.8, TAC1, CALCA, GAP43, DPYSL2, NMNAT2). Moreover, after confirming robust functional activities and differential response to noxious stimuli and specific drugs, a robotic cell culture system was employed to produce large quantities of human sensory neurons, which can be used to develop nociceptor-selective analgesics.",

keywords = "CEPT cocktail, analgesics, cell differentiation, drug testing, iPS cells, neural crest, nociceptor, opioid crisis, pain, sensory neuron",

author = "Tao Deng and Jovanovic, {Vukasin M.} and Tristan, {Carlos A.} and Claire Weber and Chu, {Pei Hsuan} and Jason Inman and Seungmi Ryu and Yogita Jethmalani and {Ferreira de Sousa}, Juliana and Pinar Ormanoglu and Prisca Twumasi and Chaitali Sen and Jaehoon Shim and Selwyn Jayakar and {Bear Zhang}, {Han Xiong} and Sooyeon Jo and Weifeng Yu and Voss, {Ty C.} and Anton Simeonov and Bean, {Bruce P.} and Woolf, {Clifford J.} and Ilyas Singe{\c c}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = apr,

day = "11",

doi = "10.1016/j.stemcr.2023.03.006",

language = "English",

volume = "18",

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Deng, T, Jovanovic, VM, Tristan, CA, Weber, C, Chu, PH, Inman, J, Ryu, S, Jethmalani, Y, Ferreira de Sousa, J, Ormanoglu, P, Twumasi, P, Sen, C, Shim, J, Jayakar, S, Bear Zhang, HX, Jo, S, Yu, W, Voss, TC, Simeonov, A, Bean, BP, Woolf, CJ & Singeç, I 2023, 'Scalable generation of sensory neurons from human pluripotent stem cells', Stem Cell Reports, vol. 18, no. 4, pp. 1030-1047. https://doi.org/10.1016/j.stemcr.2023.03.006

TY - JOUR

T1 - Scalable generation of sensory neurons from human pluripotent stem cells

AU - Deng, Tao

AU - Jovanovic, Vukasin M.

AU - Tristan, Carlos A.

AU - Weber, Claire

AU - Chu, Pei Hsuan

AU - Inman, Jason

AU - Ryu, Seungmi

AU - Jethmalani, Yogita

AU - Ferreira de Sousa, Juliana

AU - Ormanoglu, Pinar

AU - Twumasi, Prisca

AU - Sen, Chaitali

AU - Shim, Jaehoon

AU - Jayakar, Selwyn

AU - Bear Zhang, Han Xiong

AU - Jo, Sooyeon

AU - Yu, Weifeng

AU - Voss, Ty C.

AU - Simeonov, Anton

AU - Bean, Bruce P.

AU - Woolf, Clifford J.

AU - Singeç, Ilyas

PY - 2023/4/11

Y1 - 2023/4/11

N2 - Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types. Following principles of developmental biology and translational applicability, here we developed an efficient stepwise differentiation method for peptidergic and non-peptidergic nociceptors. By modulating specific cell signaling pathways, hPSCs were first converted into SOX10+ neural crest, followed by differentiation into sensory neurons. Detailed characterization, including ultrastructural analysis, confirmed that the hPSC-derived nociceptors displayed cellular and molecular features comparable to native dorsal root ganglion (DRG) neurons, and expressed high-threshold primary sensory neuron markers, transcription factors, neuropeptides, and over 150 ion channels and receptors relevant for pain research and axonal growth/regeneration studies (e.g., TRPV1, NAV1.7, NAV1.8, TAC1, CALCA, GAP43, DPYSL2, NMNAT2). Moreover, after confirming robust functional activities and differential response to noxious stimuli and specific drugs, a robotic cell culture system was employed to produce large quantities of human sensory neurons, which can be used to develop nociceptor-selective analgesics.

AB - Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types. Following principles of developmental biology and translational applicability, here we developed an efficient stepwise differentiation method for peptidergic and non-peptidergic nociceptors. By modulating specific cell signaling pathways, hPSCs were first converted into SOX10+ neural crest, followed by differentiation into sensory neurons. Detailed characterization, including ultrastructural analysis, confirmed that the hPSC-derived nociceptors displayed cellular and molecular features comparable to native dorsal root ganglion (DRG) neurons, and expressed high-threshold primary sensory neuron markers, transcription factors, neuropeptides, and over 150 ion channels and receptors relevant for pain research and axonal growth/regeneration studies (e.g., TRPV1, NAV1.7, NAV1.8, TAC1, CALCA, GAP43, DPYSL2, NMNAT2). Moreover, after confirming robust functional activities and differential response to noxious stimuli and specific drugs, a robotic cell culture system was employed to produce large quantities of human sensory neurons, which can be used to develop nociceptor-selective analgesics.

KW - CEPT cocktail

KW - analgesics

KW - cell differentiation

KW - drug testing

KW - iPS cells

KW - neural crest

KW - nociceptor

KW - opioid crisis

KW - pain

KW - sensory neuron

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DO - 10.1016/j.stemcr.2023.03.006

M3 - Article

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SN - 2213-6711

VL - 18

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JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 4

ER -

Scalable generation of sensory neurons from human pluripotent stem cells

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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