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| Status |
Public on Mar 21, 2023 |
| Title |
Neuronal identity defines a-synuclein and tau toxicity |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pathogenic a-synuclein and tau are critical drivers of neurodegeneration and their mutations cause neuronal loss in patients. Whether the underlying preferential neuronal vulnerability is a cell-type intrinsic property or a consequence of increased expression levels remains elusive. Here, we explore cell-type specific a-synuclein and tau expression in human brain datasets and use deep phenotyping as well as brain- wide single-cell RNA sequencing of >200 live neuron types in fruit flies to ask which cellular environments react most to a-synuclein or tau toxicity. We detect phenotypic and transcriptomic evidence of differential neuronal vulnerability independent of a-synuclein or tau expression levels. Comparing vulnerable with resilient neurons in Drosophila enabled us to predict numerous human neuron subtypes with increased intrinsic susceptibility to pathogenic a-synuclein or tau. By uncovering synapse and Ca2+ homeostasis related genes as tau toxicity modifiers our work paves the way to leverage neuronal identity to uncover modifiers of neurodegeneration-associated toxic proteins.
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| Overall design |
Drosophila brains at 5, 25 and 45 days were dissected, dissociated and scRNAseq performed with 10x v3.1 chemistry; GFP+ C2_3 neurons were FAC-sorted and 400 cells/sample were processed with an adapted Smart-seq3 protocol.
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| Contributor(s) |
Praschberger R, Poovathingal S, Verstreken P |
| Citation(s) |
36948206 |
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| Submission date |
Jan 24, 2023 |
| Last update date |
Jun 20, 2023 |
| Contact name |
Patrik Verstreken |
| E-mail(s) |
patrik.verstreken@kuleuven.be
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| Organization name |
VIB-KU Leuven
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| Street address |
Herestraat 49
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| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
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| Platforms (3) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
| GPL30203 |
NextSeq 2000 (Drosophila melanogaster) |
| GPL30567 |
MGISEQ-2000RS (Drosophila melanogaster) |
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| Samples (48)
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| GSM6965966 |
brain, tauP301L, 5d, rep1 |
| GSM6965967 |
brain, mini_ctrl, 5d, rep2 |
| GSM6965968 |
brain, smGdP, 5d, rep2 |
| GSM6965969 |
brain, asynA53T, 5d, rep2 |
| GSM6965970 |
brain, tauP301L, 5d, rep2 |
| GSM6965971 |
brain, mini_ctrl, 5d, rep3 |
| GSM6965972 |
brain, smGdP, 5d, rep3 |
| GSM6965973 |
brain, asynA53T, 5d, rep3 |
| GSM6965974 |
brain, tauP301L, 5d, rep3 |
| GSM6965975 |
brain, mini_ctrl, 25d, rep4 |
| GSM6965976 |
brain, smGdP, 25d, rep4 |
| GSM6965977 |
brain, asynA53T, 25d, rep4 |
| GSM6965978 |
brain, tauP301L, 25d, rep4 |
| GSM6965979 |
brain, mini_ctrl, 25d, rep5 |
| GSM6965980 |
brain, smGdP, 25d, rep5 |
| GSM6965981 |
brain, asynA53T, 25d, rep5 |
| GSM6965982 |
brain, tauP301L, 25d, rep5 |
| GSM6965983 |
brain, mini_ctrl, 25d, rep6 |
| GSM6965984 |
brain, smGdP, 25d, rep6 |
| GSM6965985 |
brain, asynA53T, 25d, rep6 |
| GSM6965986 |
brain, tauP301L, 25d, rep6 |
| GSM6965987 |
brain, mini_ctrl, 45d, rep7, sample1 |
| GSM6965988 |
brain, mini_ctrl, 45d, rep7, sample2 |
| GSM6965989 |
brain, tauP301L, 45d, rep7, sample1 |
| GSM6965990 |
brain, tauP301L, 45d, rep7, sample2 |
| GSM6965991 |
brain, mini_ctrl, 45d, rep8, sample1 |
| GSM6965992 |
brain, mini_ctrl, 45d, rep8, sample2 |
| GSM6965993 |
brain, tauP301L, 45d, rep8, sample1 |
| GSM6965994 |
brain, tauP301L, 45d, rep8, sample2 |
| GSM6965995 |
brain, mini_ctrl, 45d, rep9, sample1 |
| GSM6965996 |
brain, mini_ctrl, 45d, rep9, sample2 |
| GSM6965997 |
brain, tauP301L, 45d, rep9, sample1 |
| GSM6965998 |
brain, tauP301L, 45d, rep9, sample2 |
| GSM6965999 |
brain, mini_ctrl, 45d, rep10, sample1 |
| GSM6966000 |
brain, mini_ctrl, 45d, rep10, sample2 |
| GSM6966001 |
brain, tauP301L, 45d, rep10, sample1 |
| GSM6966002 |
brain, tauP301L, 45d, rep10, sample2 |
| GSM6966003 |
C2_3 neurons, asynA53T, 25d, sample1 |
| GSM6966004 |
C2_3 neurons, asynA53T, 25d, sample 2 |
| GSM6966005 |
C2_3 neurons, asynA53T, 25d, sample3 |
| GSM6966006 |
C2_3 neurons, asynA53T, 25d, sample4 |
| GSM6966007 |
C2_3 neurons, tauP301L, 25d, sample1 |
| GSM6966008 |
C2_3 neurons, tauP301L, 25d, sample2 |
| GSM6966009 |
C2_3 neurons, tauP301L, 25d, sample3 |
| GSM6966010 |
C2_3 neurons, tauP301L, 25d, sample4 |
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| Relations |
| BioProject |
PRJNA926993 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223626_45d_dataset_barcodes.tsv.gz |
587.1 Kb |
(ftp)(http) |
TSV |
| GSE223626_45d_dataset_genes.tsv.gz |
105.4 Kb |
(ftp)(http) |
TSV |
| GSE223626_45d_dataset_soupX_corrected.mtx.gz |
901.0 Mb |
(ftp)(http) |
MTX |
| GSE223626_45d_meta_data.tsv.gz |
3.6 Mb |
(ftp)(http) |
TSV |
| GSE223626_5_25d_dataset_barcodes.tsv.gz |
698.7 Kb |
(ftp)(http) |
TSV |
| GSE223626_5_25d_dataset_genes.tsv.gz |
105.7 Kb |
(ftp)(http) |
TSV |
| GSE223626_5_25d_dataset_soupX_corrected.mtx.gz |
1.5 Gb |
(ftp)(http) |
MTX |
| GSE223626_5_25d_dataset_uncorrected_UMI.mtx.gz |
589.7 Mb |
(ftp)(http) |
MTX |
| GSE223626_5_25d_meta_data.tsv.gz |
4.6 Mb |
(ftp)(http) |
TSV |
| GSE223626_C2_3_FACS_25d_counts.tsv.gz |
205.3 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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