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Nature, 09 April 2025 | https://doi.org/10.1038/s41586-025-08808-3
Human assembloid model of the ascending neural sensory pathway
Ji-il Kim 1,2,5, Kent Imaizumi 1,2,5, Ovidiu Jurjuț 1,2, Kevin W. Kelley 1,2, Dong Wang 1,2, Mayuri Vijay Thete 1,2, Zuzana Hudacova 1,2, Neal D. Amin 1,2, Rebecca J. Levy 3, Grégory Scherrer 4 & Sergiu P. Pașca 1,2,*
1Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
2Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute & Bio-X, Stanford, CA, USA.
3Department of Neurology & Neurological Sciences, Division of Child Neurology, Stanford University, Stanford, CA, USA.
4Department of Cell Biology and Physiology, UNC Neuroscience Center, Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
5These authors contributed equally: Ji-il Kim, Kent Imaizumi.
2Stanford Brain Organogenesis Program, Wu Tsai Neurosciences Institute & Bio-X, Stanford, CA, USA.
3Department of Neurology & Neurological Sciences, Division of Child Neurology, Stanford University, Stanford, CA, USA.
4Department of Cell Biology and Physiology, UNC Neuroscience Center, Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
5These authors contributed equally: Ji-il Kim, Kent Imaizumi.
*Corresponding author: correspondence to Sergiu P. Pașca
Abstract
Somatosensory pathways convey crucial information about pain, touch, itch and body part movement from peripheral organs to the central nervous system. Despite substantial needs to understand how these pathways assemble and to develop pain therapeutics, clinical translation remains challenging. This is probably related to species-specific features and the lack of in vitro models of the polysynaptic pathway. Here we established a human ascending somatosensory assembloid (hASA), a four-part assembloid generated from human pluripotent stem cells that integrates somatosensory, spinal, thalamic and cortical organoids to model the spinothalamic pathway. Transcriptomic profiling confirmed the presence of key cell types of this circuit. Rabies tracing and calcium imaging showed that sensory neurons connect to dorsal spinal cord neurons, which further connect to thalamic neurons. Following noxious chemical stimulation, calcium imaging of hASA demonstrated a coordinated response. In addition, extracellular recordings and imaging revealed synchronized activity across the assembloid. Notably, loss of the sodium channel NaV1.7, which causes pain insensitivity, disrupted synchrony across hASA. By contrast, a gain-of-function SCN9A variant associated with extreme pain disorder induced hypersynchrony. These experiments demonstrated the ability to functionally assemble the essential components of the human sensory pathway, which could accelerate our understanding of sensory circuits and facilitate therapeutic development.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-04-11)
- 국외 연구진
- 생명과학 > 신경생물학
관련 보도자료
美, 동물실험 폐지 수순…한국 과학자, 오가노이드로 감각신경회로 구현
9일(현지시간) 국제학술지 '네이처'에 게재된 연구 논문의 제1저자인 김지일 미국 스탠퍼드대 박사후연구원은 최근 진행한 영상 인터뷰에서 "이번 연구는 동물실험의 한계를 극복하고 인간 특이적 반응을 정밀하게 관찰할 수 있다는 점에서 학술적, 임상적으로 모두 의미가 크다"고 말했다. 특히 통증 신호 처리와 같은 복잡한 신경회로 작동 원리를 직접 연구할 수 있는 기반이 마련되면서 향후 중독 위험이 없는 맞춤형 진통제 개발에도 응용이 가능할 것으로 전망했다.
- 동아사이언스
- 2025. 04. 28
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