Fig. 7 Longitudinal single-cell RNA-seq reveals stability of PRO but not INV state. a. Schematic of experiment. Prior to flow cytometry and 10X single-cell RNA-seq, ZMEL1-PRO and -INV cells were either grown in vitro (individual or co-culture) or isolated from zebrafish orthotopically transplanted with a 1:1 mixture of PRO and INV (primary tumors or metastases). b. Uniform Manifold Approximation and Projection (UMAP) (McInnes et al., 2018) dimensionality reduction of 40,293 ZMEL1 cells sequenced as in (a). Individual culture (IND); co-culture (CO); primary tumors (PRI); metastases (MET). c. PRO and INV scores based on ZMEL1 bulk RNA-seq plotted for all cells (gray) with ZMEL1-PRO (purple) and ZMEL1-INV (green) for the indicated condition overlaid. Diagonal line represents the classifier used in (d). d. Confusion matrices comparing initial cell identity with observed cell classification based on a linear classifier trained on in vitro individual culture samples. e. ZMEL1-INV cells plotted as in (c) colored according to tfap2e mRNA expression reveal re-activation of tfap2e upon metastatic dissemination. See also Figure S7.
Reprinted from Developmental Cell, 56(20), Campbell, N.R., Rao, A., Hunter, M.V., Sznurkowska, M.K., Briker, L., Zhang, M., Baron, M., Heilmann, S., Deforet, M., Kenny, C., Ferretti, L.P., Huang, T.H., Perlee, S., Garg, M., Nsengimana, J., Saini, M., Montal, E., Tagore, M., Newton-Bishop, J., Middleton, M.R., Corrie, P., Adams, D.J., Rabbie, R., Aceto, N., Levesque, M.P., Cornell, R.A., Yanai, I., Xavier, J.B., White, R.M., Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation, 2808-2825.e10, Copyright (2021) with permission from Elsevier. Full text @ Dev. Cell