Derivation of nociceptive sensory neurons from hiPSCs with early patterning and temporally controlled NEUROG2 overexpression

Plumbly, William; Patikas, Nikolaos; Field, Sarah; Foskolou, Stefanie; Metzakopian, Emmanouil

doi:10.1016/j.crmeth.2022.100341

Cited by 8 publications

(9 citation statements)

References 56 publications

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“…MEA technology enables robust monitoring of extracellular network activities, uniformly sampled over several months, which fabricates opportunities for precise pharmacological manipulations combined with long-term activity recordings in vivo ( 24 ). Spontaneous network activity laid the infrastructure of functional networks during early central nervous system development ( 17 ). Spontaneous NBs dynamics triggered by the unique modifications of each pathway inhibitor have been observed in cultured neural networks.…”

Section: Discussionmentioning

confidence: 99%

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JNK and PI3K signaling pathways mediate synapse formation and network spontaneous activities in primary neurons

Jia,

Zhu,

et al. 2024

Preprint

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Background: Cellular signals orchestrating synapse formation and neuronal network function remain poorly understood. To explore the critical signaling pathways in neurons and their influence on network development, pharmacological assays were employed to inhibit multiple signaling pathways in cultured neurons. Methods: Immunofluorescence and western blotting are applied to identify the expression of synapse-related proteins within neurons. micro-electrode arrays (MEAs) are employed to study the developmental characteristics of neuronal networks. RNA sequencing is utilized to determine the gene expression profiles pertaining to multiple signaling pathways. Results: Canonical c-jun N-terminal kinases (JNK) pathway is necessary for pre- and post-synaptic specializations, while phosphatidylinositide3-kinases (PI3K) is a key to postsynaptic specialization and affects the puncta sizes of presynaptic marker. Unexpectedly, pharmacological inhibition of JNK pathway significantly suppressed the mean firing rate (MFR), network burst frequency (NBF) and regularity of network firing after 4 weeks, but did not alter the synchrony of the network. During network development, PI3K pathway regulates the longer burst duration and lower network synchrony. Gene sets associated with neurodevelopmental processes and myelination was disturbed during restraining these signal pathways. Furthermore, inhibition of the PI3K signaling pathway obviously transformed voltage-gated ion channel activity, synaptic transmission and synaptic plasticity of neurons. Conclusion: This study reveals that JNK and PI3K signaling pathways play different roles during synapse formation, and these signaling pathways have a lasting impact on the development of neuronal networks. Thus, this study provides further insights into the intracellular signaling pathways associated with synapse formation in the development of neuronal networks.

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Section: Discussionmentioning

confidence: 99%

“…Using the 6-well MEA system (AXION Biosystems, Maestro Pro, America), all recordings were conducted as previously described ( 17 ). These MEA devices facilitate non-invasive recording of neuronal activity simultaneously at multiple nodes within the same network.…”

Section: Methodsmentioning

confidence: 99%

JNK and PI3K signaling pathways mediate synapse formation and network spontaneous activities in primary neurons

Jia,

Zhu,

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…MEA technology enables robust monitoring of extracellular network activities, uniformly sampled over several months, which fabricates opportunities for precise pharmacological manipulations combined with long-term activity recordings in vivo (24). Spontaneous network activity laid the infrastructure of functional networks during early central nervous system development (17). Spontaneous NBs dynamics triggered by the unique modi cations of each pathway inhibitor have been observed in cultured neural networks.…”

Section: Discussionmentioning

confidence: 99%

JNK and PI3K signaling pathways mediate synapse formation and network spontaneous activities in primary neurons

Jia,

Jiang,

Zhu

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Cellular signals orchestrating synapse formation and neuronal network function remain poorly understood. To explore the critical signaling pathways in neurons and their influence on network development, pharmacological assays were employed to inhibit multiple signaling pathways in cultured neurons. Methods Immunofluorescence and western blotting are applied to identify the expression of synapse-related proteins within neurons. micro-electrode arrays (MEAs) are employed to study the developmental characteristics of neuronal networks. RNA sequencing is utilized to determine the gene expression profiles pertaining to multiple signaling pathways. Results Canonical c-jun N-terminal kinases (JNK) pathway is necessary for pre- and post-synaptic specializations, while phosphatidylinositide3-kinases (PI3K) is a key to postsynaptic specialization and affects the puncta sizes of presynaptic marker. Unexpectedly, pharmacological inhibition of JNK pathway significantly suppressed the mean firing rate (MFR), network burst frequency (NBF) and regularity of network firing after 4 weeks, but did not alter the synchrony of the network. During network development, PI3K pathway regulates the longer burst duration and lower network synchrony. Gene sets associated with neurodevelopmental processes and myelination was disturbed during restraining these signal pathways. Furthermore, inhibition of the PI3K signaling pathway obviously transformed voltage-gated ion channel activity, synaptic transmission and synaptic plasticity of neurons. Conclusion This study reveals that JNK and PI3K signaling pathways play different roles during synapse formation, and these signaling pathways have a lasting impact on the development of neuronal networks. Thus, this study provides further insights into the intracellular signaling pathways associated with synapse formation in the development of neuronal networks.

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“…[4] iPSC-derived sensory neurons: scRNA-seq/10x sequencing was conducted in nociceptive sensory neurons induced from iPSCs (Plumbly et al, 2022).…”

Section: Human Subjects Who Contributed To the Nasal Biopsymentioning

confidence: 99%

Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

Yang

Ishizuka

Lane

et al. 2022

Preprint

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Biopsy is an essential procedure of clinical medicine in which we obtain tissues and cells that are supposed to directly reflect pathological changes of each disease. Biopsy from the brain is difficult at both practical and ethical levels. Nasal biopsy that captures tissues with olfactory neurons has been considered as an alternative method of obtaining neurons from living patients with brain disorders. However, insufficient characterization of biopsied cells/tissues has hampered a wider use of nasal tissues as surrogate resources for the brain. By conducting single cell and bulk RNA-sequence analysis of olfactory neuronal cells (ONCs) enriched from nasal biopsied tissues and using multiple pubic datasets in comparison, we now report precise characterization of ONCs at the molecular levels. These cells are easily and reproducibly prepared and have two major strengths. They are homogeneous and neuronal, resembling excitatory neurons in the dorsolateral prefrontal cortex and anterior cingulate cortex in molecular signatures.

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Derivation of nociceptive sensory neurons from hiPSCs with early patterning and temporally controlled NEUROG2 overexpression

Cited by 8 publications

References 56 publications

JNK and PI3K signaling pathways mediate synapse formation and network spontaneous activities in primary neurons

JNK and PI3K signaling pathways mediate synapse formation and network spontaneous activities in primary neurons

JNK and PI3K signaling pathways mediate synapse formation and network spontaneous activities in primary neurons

Human olfactory neuronal cells through nasal biopsy: molecular characterization and utility in brain science

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