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| Status |
Public on Jan 01, 2020 |
| Title |
Distinct SOX signature determines neuroblastoma origin and predicts clinical outcome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Multimodality treatment of high-risk neuroblastoma can be effective, but up to 50% of children experience recurrent disease with fatal outcome. Extensive genetic intratumoral heterogeneity and diverse clinical outcomes pose therapeutic challenges in treating children affected by this aggressive disease. Several hypotheses have been proposed to explain the heterogeneity of neuroblastoma, including a possible origin from multipotent neural crest stem cells (NCSCs). Utilizing an in vivo mouse genetics approach, we demonstrate that lineage-restricted sympathoadrenal (SA) progenitors and not NCSCs are the cellular origin of neuroblastoma. Human neuroblastoma tissue is composed of two spatially juxtaposed cell types, neuroblasts and Schwann cells, both cell types derive from neural crest (NC) lineage. This composition mimics the architecture of sympathetic ganglions (SG) as well as of adrenal medulla at the late stage of neural crest (NC) development. Similarly to SG, SOX10 is restricted to Schwannian cells and is not present in tumorigenic neuroblasts. Transcriptional landscape of Sox genes can serve as paradigmatic model for stage identification along NC lineage development. While early multipotent NCSCs are characterized by the expression of Sox9/Sox10 transcription factors (TF), committed SA progenitor identity is defined by the presence of Sox4/Sox11 TFs. Molecularly, we show that the core transcriptional network that orchestrate neuroblastoma maintenance is highly reminiscent of the SA progenitors. Taken together, the data presented here show that neuroblastoma cells functionally resemble the committed SA progenitors, while lacking specific stem cell program.
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| Overall design |
RNA-seq of human neuroblastoma cell lines overexpress or knockdown SOX9
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| |
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| Contributor(s) |
Yang C, Serra-Roma A, Shakhova O |
| Citation(s) |
32595833 |
| Submission date |
Jun 19, 2019 |
| Last update date |
Jul 15, 2020 |
| Contact name |
giancarlo russo |
| E-mail(s) |
giancarlo.russo@fgcz.ethz.ch
|
| Organization name |
ETH/University of Zurich
|
| Department |
Functional Genomics Center Zurich
|
| Street address |
winterthurerstrasse 190
|
| City |
Zurich |
| State/province |
Schweiz |
| ZIP/Postal code |
8057 |
| Country |
Switzerland |
| |
|
| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (18)
|
|
| Relations |
| BioProject |
PRJNA549698 |
| SRA |
SRP201900 |
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