PROJECT ID: PRJNA641144

Data source SRA: PRJNA641144
Description We report single-cell gene expression profiling of the zebrafish melanoma cell lines ZMEL1-PRO and ZMEL1-INV under multiple in vitro and in vivo (zebrafish transplant) conditions
Key word epithelial-mesenchymal transition; breast-cancer metastasis; neural crest; in-vivo; differentiation program; transcription factors; expression; plasticity; zebrafish; heterogeneity
Publication Campbell NR, Rao A, Hunter MV, Sznurkowska MK et al. Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation. Dev Cell 2021 Oct 25;56(20):2808-2825.e10. PMID: 34529939
Abstract Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) sub populations that represent a "go or grow"trade-off; however, how these populations interact is poorly understood. Using a combination of zebrafish modeling and analysis of patient samples, we show that INV and PRO cells form spatially structured heterotypic clusters and cooperate in the seeding of metastasis, maintaining cell state heterogeneity. INV cells adhere tightly to each other and form clusters with a rim of PRO cells. Intravital imaging demonstrated cooperation in which INV cells facilitate dissemination of less metastatic PRO cells. We identified the TFAP2 neural crest transcription factor as a master regulator of clustering and PRO/INV states. Isolation of clusters from patients with metastatic melanoma revealed a subset with heterotypic PRO-INV clusters. Our data suggest a framework for the co-existence of these two divergent cell populations, in which heterotypic clusters promote metastasis via cell-cell cooperation.


Dataset Information

Dataset ID Species Tissue / Organ Experiment type Sample Source dataset ID
1. PRJNA641144 (P_INV) Danio rerio tumor disease adult, ZMEL1-INV cells in vivo primary tumors SRA: SRR12070722
2. PRJNA641144 (P_PRO) Danio rerio tumor disease adult, ZMEL1-PRO cells in vivo primary tumors SRA: SRR12070742
3. PRJNA641144 (M_INV) Danio rerio tumor disease adult, ZMEL1-INV cells in vivo metastases SRA: SRR12070746
4. PRJNA641144 (M_PRO) Danio rerio tumor disease adult, ZMEL1-PRO cells in vivo metastases SRA: SRR12070758
5. PRJNA641144 (D_INV) Danio rerio tumor disease adult, ZMEL1-INV cells in vitro individual culture SRA: SRR12070771
6. PRJNA641144 (D_PRO) Danio rerio tumor disease adult, ZMEL1-PRO cells in vitro individual culture SRA: SRR12070788
7. PRJNA641144 (C_INV) Danio rerio tumor disease adult, ZMEL1-INV cells in vitro co-culture SRA: SRR12070794
8. PRJNA641144 (C_PRO) Danio rerio tumor disease adult, ZMEL1-PRO cells in vitro co-culture SRA: SRR12070806

Clustering Result

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
5 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
6 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
7 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
8 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
5 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
6 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
7 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
5 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
6 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
7 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
8 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
5 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
6 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
7 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
8 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
5 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
5 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018

Cluster Cell type Gene id (symbol) Marker class Evidence
1 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
2 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
3 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018
4 Melanoma cells ENSDARG00000077467 (sox10) marker DOI:10.1016/j.devcel.2021.08.018