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| Status |
Public on Dec 09, 2022 |
| Title |
Evidence of shared transcriptomic dysregulation of HNRNPU-related disorder between human organoids and embryonic mice |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Generating effective therapies for neurodevelopmental disorders has remained elusive. An emerging drug discovery approach for neurodevelopmental disorders is to characterize transcriptome wide dysregulation in an appropriate model system and screen therapeutics based on their capacity to restore functionally relevant expression patterns. We characterized transcriptomic dysregulation in a human model of HNRNPU-related disorder to explore the potential of such a paradigm. We identified widespread dysregulation in functionally relevant pathways and then compared dysregulation in a human model to transcriptomic differences in embryonic and perinatal mice to determine whether dysregulation in an in vitro human model is partially replicated in an in vivo model of HNRNPU-related disorder. Strikingly, we find enrichment of co-dysregulation between 45-day-old human organoids and embryonic, but not perinatal, mice from distinct models of HNRNPU-related disorder. Thus, hnRNPU deficient human organoids may only be suitable to model transcriptional dysregulation in certain cell types within a specific developmental time window.
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| Overall design |
Single-cell RNA-sequencing experiments (Experiment 1 - three human cortical organoid lines (PGP1 control, D11 HNRNPU KO, M20 HNRNPU het KO different mutation) with three samples per line. Experiment 2 - Same three lines with organoids same age, two samples per line from differentiations beginning at a later date). Bulk RNA-sequencing experiments - three experiments deposited. Hnrnpu constitutive het KO at E13 (3 HET, 4 WT mice) and at P0 (4 litters, 2 experiments, 7 HET, 4 WT mice). Hnrnpu conditional truncating mutation in Emx1+ cells at P1 (3 litters, 3 HOM, 4 HET, 5 WT mice).
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| Contributor(s) |
Ressler AK |
| Citation(s) |
36594023 |
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| Submission date |
Dec 02, 2022 |
| Last update date |
Jan 11, 2023 |
| Contact name |
Andrew K Ressler |
| E-mail(s) |
akr2151@cumc.columbia.edu, aress212@gmail.com
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| Organization name |
Columbia University
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| Street address |
701 w 168th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (50)
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| GSM6782314 |
hCOs_scRNA_expt1_D11_1 |
| GSM6782315 |
hCOs_scRNA_expt1_D11_2 |
| GSM6782316 |
hCOs_scRNA_expt1_D11_3 |
| GSM6782317 |
hCOs_scRNA_expt1_M20_1 |
| GSM6782318 |
hCOs_scRNA_expt1_M20_2 |
| GSM6782319 |
hCOs_scRNA_expt1_M20_3 |
| GSM6782320 |
hCOs_scRNA_expt2_PGP1_4 |
| GSM6782321 |
hCOs_scRNA_expt2_PGP1_5 |
| GSM6782322 |
hCOs_scRNA_expt2_D11_4 |
| GSM6782323 |
hCOs_scRNA_expt2_D11_5 |
| GSM6782324 |
hCOs_scRNA_expt2_M20_4 |
| GSM6782325 |
hCOs_scRNA_expt2_M20_5 |
| GSM6782326 |
DGAR1, bulkRNA |
| GSM6782327 |
DGAR2, bulkRNA |
| GSM6782328 |
DGAR3, bulkRNA |
| GSM6782329 |
DGAR4, bulkRNA |
| GSM6782330 |
DGAR5, bulkRNA |
| GSM6782331 |
DGAR6, bulkRNA |
| GSM6782332 |
DGAR7, bulkRNA |
| GSM6782333 |
ARNS2, bulkRNA |
| GSM6782334 |
ARNS3, bulkRNA |
| GSM6782335 |
ARNS4, bulkRNA |
| GSM6782336 |
ARNS5, bulkRNA |
| GSM6782337 |
ARNS6, bulkRNA |
| GSM6782338 |
ARNS7, bulkRNA |
| GSM6782339 |
ARNS8, bulkRNA |
| GSM6782340 |
sdmusrnaseq401, bulkRNA |
| GSM6782341 |
sdmusrnaseq4010, bulkRNA |
| GSM6782342 |
sdmusrnaseq4011, bulkRNA |
| GSM6782343 |
sdmusrnaseq402, bulkRNA |
| GSM6782344 |
sdmusrnaseq404, bulkRNA |
| GSM6782345 |
sdmusrnaseq406, bulkRNA |
| GSM6782346 |
sdmusrnaseq412, bulkRNA |
| GSM6782347 |
sdmusrnaseq413, bulkRNA |
| GSM6782348 |
sdmusrnaseq414, bulkRNA |
| GSM6782349 |
AKR21, bulkRNA |
| GSM6782350 |
AKR24, bulkRNA |
| GSM6782351 |
AKR25, bulkRNA |
| GSM6782352 |
AKR26, bulkRNA |
| GSM6782353 |
AKR27, bulkRNA |
| GSM6782354 |
AKR28, bulkRNA |
| GSM6782355 |
AKR31, bulkRNA |
| GSM6782356 |
AKR33, bulkRNA |
| GSM6782357 |
AKR34, bulkRNA |
| GSM6782358 |
AKR37, bulkRNA |
| GSM6782359 |
AKR38, bulkRNA |
| GSM6782360 |
AKR39, bulkRNA |
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| Relations |
| BioProject |
PRJNA907875 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE219317_E13_Hnrnpu+-.csv.gz |
922.3 Kb |
(ftp)(http) |
CSV |
| GSE219317_P0_Hnrnpu+-.csv.gz |
920.5 Kb |
(ftp)(http) |
CSV |
| GSE219317_P1_Hnrnpu_fl_het.csv.gz |
886.3 Kb |
(ftp)(http) |
CSV |
| GSE219317_P1_Hnrnpu_fl_hom.csv.gz |
924.8 Kb |
(ftp)(http) |
CSV |
| GSE219317_RAW.tar |
1.7 Gb |
(http)(custom) |
TAR (of H5) |
| GSE219317_SampleDescriptions.csv.gz |
422 b |
(ftp)(http) |
CSV |
| GSE219317_Seurat_Robject.RData.gz |
3.6 Gb |
(ftp)(http) |
RDATA |
| GSE219317_est_counts_genes_kallisto_E13_HNRNPU+-.txt.gz |
362.7 Kb |
(ftp)(http) |
TXT |
| GSE219317_est_counts_genes_kallisto_P0_HNRNPU+-.txt.gz |
602.2 Kb |
(ftp)(http) |
TXT |
| GSE219317_est_counts_genes_kallisto_P0_HNRNPUfl-andflfl.txt.gz |
501.6 Kb |
(ftp)(http) |
TXT |
| GSE219317_hnrnpu_exp1and2_integrated_nfeatures2000_mtregress_dims11_respoint5_mt_umi.RData.gz |
3.6 Gb |
(ftp)(http) |
RDATA |
| GSE219317_orgDEGs.xlsx |
605.4 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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