TY - JOUR
T1 - Single-Cell Profiling Uncovers Evolutionary Divergence of Hypocretin/Orexin Neuronal Subpopulations
AU - Sagi, Dana
AU - Tibi, Muhammad
AU - Admati, Inbal
AU - Lerer-Goldshtein, Tali
AU - Hochgerner, Hannah
AU - Zeisel, Amit
AU - Appelbaum, Lior
N1 - Publisher Copyright:
Copyright © 2024 the authors.
PY - 2024/9/4
Y1 - 2024/9/4
N2 - Brain nuclei are traditionally defined by their anatomy, activity, and expression of specific markers. The hypothalamus contains discrete neuronal populations that coordinate fundamental behavioral functions, including sleep and wakefulness, in all vertebrates. Particularly, the diverse roles of hypocretin/orexin (Hcrt)-releasing neurons suggest functional heterogeneity among Hcrt neurons. Using single-cell RNA sequencing (scRNA-seq) and high-resolution imaging of the adult male and female zebrafish hypothalamic periventricular zone, we identified 21 glutamatergic and 28 GABAergic cell types. Integration of zebrafish and mouse scRNA-seq revealed evolutionary conserved and divergent hypothalamic cell types. The expression of specific genes, including npvf, which encodes a sleep-regulating neuropeptide, was enriched in subsets of glutamatergic Hcrt neurons in both larval and adult zebrafish. The genetic profile, activity, and neurite processing of the neuronal subpopulation that coexpresses both Hcrt and Npvf (Hcrt+Npvf+) differ from other Hcrt neurons. These interspecies findings provide a unified annotation of hypothalamic cell types and suggest that the heterogeneity of Hcrt neurons enables multifunctionality, such as consolidation of both wake and sleep by the Hcrt- and Npvf-releasing neuronal subpopulation.
AB - Brain nuclei are traditionally defined by their anatomy, activity, and expression of specific markers. The hypothalamus contains discrete neuronal populations that coordinate fundamental behavioral functions, including sleep and wakefulness, in all vertebrates. Particularly, the diverse roles of hypocretin/orexin (Hcrt)-releasing neurons suggest functional heterogeneity among Hcrt neurons. Using single-cell RNA sequencing (scRNA-seq) and high-resolution imaging of the adult male and female zebrafish hypothalamic periventricular zone, we identified 21 glutamatergic and 28 GABAergic cell types. Integration of zebrafish and mouse scRNA-seq revealed evolutionary conserved and divergent hypothalamic cell types. The expression of specific genes, including npvf, which encodes a sleep-regulating neuropeptide, was enriched in subsets of glutamatergic Hcrt neurons in both larval and adult zebrafish. The genetic profile, activity, and neurite processing of the neuronal subpopulation that coexpresses both Hcrt and Npvf (Hcrt+Npvf+) differ from other Hcrt neurons. These interspecies findings provide a unified annotation of hypothalamic cell types and suggest that the heterogeneity of Hcrt neurons enables multifunctionality, such as consolidation of both wake and sleep by the Hcrt- and Npvf-releasing neuronal subpopulation.
KW - cross-species integration
KW - hypocretin
KW - hypothalamus
KW - single-cell transcriptomics
KW - sleep
KW - zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85203419115&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.0095-24.2024
DO - 10.1523/jneurosci.0095-24.2024
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C2 - 39122556
AN - SCOPUS:85203419115
SN - 0270-6474
VL - 44
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 36
M1 - e0095242024
ER -