PROJECT ID: PRJNA668529

Data source SRA: PRJNA668529
Description Single Cell Olfactory Organ of Zebrafish exposed to r-Spike from SARS-CoV-2
Key word animal models; eog; olfactory damage; olfactory receptor expression; sars-cov-2; spike protein; zebrafish (Danio rerio)
Publication Kraus, Aurora, et al. "Intranasal delivery of SARS-CoV-2 Spike protein is sufficient to cause olfactory damage, inflammation and olfactory dysfunction in zebrafish." Brain, Behavior, and Immunity (2022).
Abstract Anosmia, loss of smell, is a prevalent symptom of SARS-CoV-2 infection. Anosmia may be explained by several mechanisms driven by infection of non-neuronal cells and damage in the nasal epithelium rather than direct infection of olfactory sensory neurons (OSNs). Previously, we showed that viral proteins are sufficient to cause neuroimmune responses in the teleost olfactory organ (OO). We hypothesize that SARS-CoV-2 spike (S) protein is sufficient to cause olfactory damage and olfactory dysfunction. Using an adult zebrafish model, we report that intranasally delivered SARS-CoV-2 S RBD mostly binds to the non-sensory epithelium of the olfactory organ and causes severe olfactory histopathology characterized by loss of cilia, hemorrhages and edema. Electrophysiological recordings reveal impaired olfactory function to both food and bile odorants in animals treated intranasally with SARS-CoV-2 S RBD. However, no loss of behavioral preference for food was detected in SARS-CoV-2 S RBD treated fish. Single cell RNA-Seq of the adult zebrafish olfactory organ indicated widespread loss of olfactory receptor expression and inflammatory responses in sustentacular, endothelial, and myeloid cell clusters along with reduced numbers of Tregs. Combined, our results demonstrate that intranasal SARS-CoV-2 S RBD is sufficient to cause structural and functional damage to the zebrafish olfactory system. These findings may have implications for intranasally delivered vaccines against SARS-CoV-2.


Dataset Information

Dataset ID Species Tissue / Organ Experiment type Sample Source dataset ID
1. PRJNA668529 (3d) Danio rerio olfactory rosette disease 3mpf, intranasal 100ng r-Spike 3 days SRA: SRR12858254
2. PRJNA668529 (3h) Danio rerio olfactory rosette disease 3mpf, intranasal 100ng r-Spike 3 hours SRA: SRR12858255
3. PRJNA668529 (control) Danio rerio olfactory rosette baseline 3mpf, intranasal PBS SRA: SRR12858259

Clustering Result

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Lymphocyte cells ENSDARG00000055186 (ccr9a) marker DOI:10.1007/s00251-007-0250-6, DOI:10.1016/j.bbi.2022.03.006
2 Basal cells ENSDARG00000058371 (krt5) marker DOI:10.1073/pnas.1620664114, DOI:10.1016/j.bbi.2022.03.006
2 Basal cells ENSDARG00000035809 (col1a1b) marker DOI:10.1016/j.bbi.2022.03.006
3 Neuron ENSDARG00000099744 (gap43) marker DOI:10.1016/j.bbi.2022.03.006
3 Neuron ENSDARG00000019566 (neurod1) marker DOI:10.1016/j.bbi.2022.03.006
4 Neuronal progenitor ENSDARG00000103117 (tmprss4a) marker DOI:10.1016/j.bbi.2022.03.006
5 Ciliated olfactory sensory neuron ENSDARG00000032380 (ompb) marker DOI:10.1073/pnas.93.18.9858, DOI:10.1016/j.bbi.2022.03.006
5 Ciliated olfactory sensory neuron ENSDARG00000105218 (ompa) marker DOI:10.1073/pnas.93.18.9858, DOI:10.1016/j.bbi.2022.03.006
6 Neuronal precursor cells ENSDARG00000028335 (hmga1a) marker DOI:10.1155/2018/3698078, DOI:10.1016/j.bbi.2022.03.006
7 Endothelium ENSDARG00000030125 (sox7) marker DOI:10.3389/fcvm.2019.00030, DOI:10.1016/j.bbi.2022.03.006
8 Microvillus olfactory sensory neuron ENSDARG00000003344 (trpc2b) marker DOI:10.1186/1471-2148-8-48, DOI:10.1016/j.bbi.2022.03.006
8 Microvillus olfactory sensory neuron ENSDARG00000038729 (s100z) marker DOI:10.1186/1471-2148-8-48, DOI:10.1016/j.bbi.2022.03.006
9 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314, DOI:10.1016/j.bbi.2022.03.006
10 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314, DOI:10.1016/j.bbi.2022.03.006
11 T cells ENSDARG00000015752 (zap70) marker DOI:10.4049/jimmunol.171.1.15, DOI:10.1016/j.bbi.2022.03.006
15 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314, DOI:10.1016/j.bbi.2022.03.006
16 Neuronal progenitor ENSDARG00000077573 (tmprss13b) marker DOI:10.1016/j.bbi.2022.03.006
17 Myeloid cells ENSDARG00000104474 (il6r) marker DOI:10.1016/j.bbi.2022.03.006

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Ciliated olfactory sensory neuron ENSDARG00000032380 (ompb) marker DOI:10.1073/pnas.93.18.9858, DOI:10.1016/j.bbi.2022.03.006
2 Lymphocyte cells ENSDARG00000055186 (ccr9a) marker DOI:10.1007/s00251-007-0250-6, DOI:10.1016/j.bbi.2022.03.006
3 Endothelium ENSDARG00000030125 (sox7) marker DOI:10.1016/j.bbi.2022.03.006
4 Basal cells ENSDARG00000058371 (krt5) marker DOI:10.1073/pnas.1620664114, DOI:10.1016/j.bbi.2022.03.006
4 Basal cells ENSDARG00000068288 (lamc2) marker DOI:10.1016/j.bbi.2022.03.006
4 Basal cells ENSDARG00000035809 (col1a1b) marker DOI:10.1016/j.bbi.2022.03.006
5 Microvillus olfactory sensory neuron ENSDARG00000003344 (trpc2b) marker DOI:10.1186/1471-2148-8-48, DOI:10.1016/j.bbi.2022.03.006
5 Microvillus olfactory sensory neuron ENSDARG00000038729 (s100z) marker DOI:10.1186/1471-2148-8-48, DOI:10.1016/j.bbi.2022.03.006
6 Neuron ENSDARG00000099744 (gap43) marker DOI:10.1016/j.bbi.2022.03.006
6 Neuron ENSDARG00000077811 (sox11a) marker DOI:10.1016/j.bbi.2022.03.006
6 Neuron ENSDARG00000095743 (sox11b) marker DOI:10.1016/j.bbi.2022.03.006
7 Endothelium ENSDARG00000030125 (sox7) marker DOI:10.3389/fcvm.2019.00030, DOI:10.1016/j.bbi.2022.03.006
8 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314120, DOI:10.1016/j.bbi.2022.03.006
10 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314120, DOI:10.1016/j.bbi.2022.03.006
11 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314120, DOI:10.1016/j.bbi.2022.03.006
15 Myeloid cells ENSDARG00000104474 (il6r) marker DOI:10.1016/j.bbi.2022.03.006

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Ciliated olfactory sensory neuron ENSDARG00000032380 (ompb) marker DOI:10.1073/pnas.93.18.9858, DOI:10.1016/j.bbi.2022.03.006
2 Lymphocyte cells ENSDARG00000055186 (ccr9a) marker DOI:10.1007/s00251-007-0250-6, DOI:10.1016/j.bbi.2022.03.006
3 Microvillus olfactory sensory neuron ENSDARG00000003344 (trpc2b) marker DOI:10.1186/1471-2148-8-48, DOI:10.1016/j.bbi.2022.03.006
3 Microvillus olfactory sensory neuron ENSDARG00000038729 (s100z) marker DOI:10.1186/1471-2148-8-48, DOI:10.1016/j.bbi.2022.03.006
4 Endothelium ENSDARG00000058358 (krt8) marker DOI:10.1016/j.bbi.2022.03.006
5 Neuron ENSDARG00000099744 (gap43) marker DOI:10.1016/j.bbi.2022.03.006
6 Basal cells ENSDARG00000058371 (krt5) marker DOI:10.1073/pnas.1620664114, DOI:10.1016/j.bbi.2022.03.006
6 Basal cells ENSDARG00000035809 (col1a1b) marker DOI:10.1073/pnas.1620664114, DOI:10.1016/j.bbi.2022.03.006
7 Endothelium ENSDARG00000030125 (sox7) marker DOI:10.3389/fcvm.2019.00030, DOI:10.1016/j.bbi.2022.03.006
8 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314120, DOI:10.1016/j.bbi.2022.03.006
12 Macrophages ENSDARG00000055290 (mpeg1.1) marker DOI:10.1182/blood-2010-10-314120, DOI:10.1016/j.bbi.2022.03.006