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| Status |
Public on Aug 30, 2019 |
| Title |
Single-cell RNA-seq Reveals a Developmental Hierarchy and Oncogenic Networks for Initiation of Medulloblastoma [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
By utilizing single-cell analysis at different stages of tumorigenesis, we demonstrated a developmental hierarchy of dynamic progenitor pools in murine sonic hedgehog-(SHH) MBs. We identified Olig2+ progenitors as transit-amplifying cells during initial tumorigenic phases. These cells are quiescent stem-like progenitors in full-blown tumors but enriched in therapy-resistant as well as recurrent medulloblastomas. Olig2 ablation or depletion of mitotic Olig2+ progenitors abrogated tumorigenesis. Transcriptome profiling and chromatin occupancy assays revealed that Olig2 activates oncogenic networks including HIPPO- Yap/Taz signaling and Aurora-A/MycN pathways. Co-targeting these oncogenic pathways induced sustained tumor growth arrest. Together, our single-cell analyses uncover unexpected glia-lineage-related Olig2+ progenitor pools critical for medulloblastoma initiation and suggest targeting Olig2-regulated oncogenic pathways as an avenue for therapy.
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| Overall design |
10 RNA-Seq samples from normal cerebellum and medullablastoma tissues (RNA_CB_1, RNA_CB_2, RNA_CB_3, RNA_Lats12cko_1, RNA_Lats12cko_2, RNA_Lats12cko_3, RNA_GFAP_Ptch_1, RNA_GFAP_Ptch_2, RNA_GFAP_Ptch_Olig2_1, RNA_GFAP_Ptch_Olig2_2)
6 RNA-Seq samples from Olig2-GFP+ cells and Olig2-GFP- cells sorted from tumor tissues of hGFAPcre;Ptchc/c;Olig2-GFP mice (RNA_Olig2-GFP+_1, RNA_Olig2-GFP+_2, RNA_Olig2-GFP+_3, RNA_Olig2-GFP-_1, RNA_Olig2-GFP-_2, RNA_Olig2-GFP-_3)
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| Contributor(s) |
Zhang L, He X, Lu R |
| Citation(s) |
31474569 |
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| Submission date |
Oct 09, 2018 |
| Last update date |
Nov 29, 2019 |
| Contact name |
Richard Lu |
| Organization name |
Cincinnati Children's Hospital Medical Center
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| Department |
CBDI
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| Lab |
Lu Lab,T6.525
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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 (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE120974 |
Single-cell RNA-seq Reveals a Developmental Hierarchy and Oncogenic Networks for Initiation of Medulloblastoma |
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| Relations |
| BioProject |
PRJNA495712 |
| SRA |
SRP165178 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120973_RAW.tar |
12.5 Mb |
(http)(custom) |
TAR (of FPKM_TRACKING) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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