Human assembloid model of the ascending neural sensory pathway
2025
Stanford University, Stanford, USA
Understanding the mechanisms underlying the development of the human sensory system is crucial for comprehending and treating sensory-related disorders. In the present study, a novel in vitro model of the ascending somatosensory pathway was developed. This model is based on a four-part assembloid generated from human pluripotent stem cells. The assembloid integrates somatosensory, spinal, thalamic, and cortical organoids to model the spinothalamic tract. Transcriptome analysis confirmed the presence of key cell types of this neuronal network. Rabies tracing and calcium imaging demonstrated that sensory neurons connect to dorsal spinal cord neurons, which in turn connect to thalamic neurons. Following noxious chemical stimulation, calcium imaging of the assembloid revealed a coordinated response. Furthermore, extracellular recordings and imaging indicated synchronized activity within the assembloid. Loss of a sodium channel, associated with pain insensitivity, disrupted synchrony throughout the assembloid, whereas a gain-of-function variant of the SCN9A gene, linked to extreme pain conditions, induced hypersynchrony. The establishment of this model could contribute to an improved understanding of sensory circuits and facilitate the development of therapies.
Human assembloid model of the ascending neural sensory pathway
Sergiu P. Paşca
Added on: 05-02-2025
[1] https://www.nature.com/articles/s41586-025-08808-3#Sec8[2] https://biermann-medizin.de/in-vitro-modell-menschlicher-nervenbahn-zur-untersuchung-von-schmerzen/
