Spatial and single-cell transcriptomic atlas of human suprachiasmatic nucleus

Feb 20, 2026Neuron

Detailed gene activity map of the human brain’s internal clock control center

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Abstract

Seven distinct neuron subtypes were identified in the adult human suprachiasmatic nucleus (SCN).

The adult human SCN has a comprehensive molecular and cellular atlas derived from advanced transcriptomics and histological analysis.
Specific transcriptomes and spatial distributions characterize each of the identified neuron subtypes within the human SCN.
Functional segregation in the SCN is conserved among humans, mice, and non-human primates, influenced by certain regulatory factors.
The human SCN exhibits significant reorganization in its neuropeptide signaling network compared to other species.
A link was found between the arginine vasopressin/neuromedin S neuron subtype and morningness chronotype in humans.

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The suprachiasmatic nucleus (SCN) is considered the master pacemaker of the circadian clock in mammals, but our current knowledge of the SCN is mostly based on rodent studies. Here, we report a comprehensive molecular and cellular atlas for the adult human SCN by spatial transcriptomics, single-nucleus RNA sequencing, and deep-learning-based histological analysis. We identified seven human SCN neuron subtypes with specific transcriptomes and spatial distributions. Comparison of humans, mice, and non-human primates revealed the conserved functional segregation within the SCN regulated by LIM homeobox 1 (LHX1) and RAR-related orphan receptor B (RORB). Furthermore, our results suggested that the human SCN has undergone marked reorganization of its neuropeptide signaling network. Finally, integrative analysis of human SCN transcriptomes and genome-wide association studies (GWASs) identified arginine vasopressin (AVP)/neuromedin S (NMS) subtype as the potential neuronal correlate for morningness chronotype. Thus, our spatial and single-cell transcriptomic atlas of the human SCN provided a basis for the understanding of neural and molecular mechanisms of the human circadian clock.

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