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| Status |
Public on Oct 08, 2022 |
| Title |
Single cell transcriptional and chromatin accessibility profiling identify the cellular heterogeneity of human medulloblastoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
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| Summary |
We report the application of single-molecule-based sequencing technology for high-throughput profiling of chromosome occupation and single cell gene expression or single nuclei chromatin accessibility in medulloblastoma tissues or cells. To further define the cellular identity at the single cell level, we characterized 26 MB tissues including 18 newly diagnosed MB tumor tissues by single cell scRNA-seq and scATAC-seq (the assay for transposase-accessible chromatin-sequencing) together with 8 previously reported MB single cell transcriptomics. The newly diagnosed MB tumors included four SHH-MBs (45,731 cells), nine G3-MBs (82,834 cells), thirteen G4 MBs (77,521 cells) with a median of 7,926 cells for scRNA-seq and 9,342 cells for scATAC-seq per MB tumor, respectively. To decipher how dynamic accessibility at the cis-regulatory elements (CREs) relates to the gene regulatory program in TCP-like cells from G3- and G4- MBs, we performed single nuclei ATAC-seq (snATAC-seq) to determine the single-cell chromatin accessibility landscape using high-quality nuclei from a set of fresh G3 and G4 MB tumors that matched with scRNA-seq. Finally, we show that gene expression with chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. Our studies identified a human-specific intermediate progenitor population important for cerebellar neural lineage development and the growth and metastasis of aggressive MBs, highlighting potential therapeutic targets.
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| Overall design |
Examination of single cell transcriptional and ATAC profiling in 3 human medulloblastoma tissues. Cut&run of 4 antibody for 2 cells
To comprehensively explore the 3D genome architecture of human aggressive medulloblastomas and to assess the contributions of genome architecture to transcriptional regulation across subgroups, we performed comparative analyses of high-throughput chromosome conformation capture (Hi-C) in medulloblastoma patient derived tumor cells, including Group 3 MB cells MB-004 and Group 4 MB cells UPN3550. We performed the Hi-C experiments in these 2 cells
Please note that the processed data file (along with the data processing description) has been updated for the GSM5952337 sample on April 26, 2023.
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| Contributor(s) |
Luo Z, Zhao C, Xin D, Lu QR |
| Citation(s) |
36450980 |
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| Submission date |
Mar 14, 2022 |
| Last update date |
Apr 26, 2023 |
| Contact name |
Zaili Luo |
| Organization name |
CCHMC
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| Lab |
Richard Lu
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| Street address |
3333 Burnet Ave.
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA816052 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE198565_RAW.tar |
12.3 Gb |
(http)(custom) |
TAR (of BED, BW, HIC, MTX, RDS, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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