Single-cell multi-omics identifies clinically relevant mesenchymal stem-like cells and key regulators for MPNST malignancy 0 Visualizations
Malignant peripheral nerve sheath tumors (MPNSTs) are devastating Schwann cell (SC)-derived peripheral nerve malignancies, often transformed from benign neurofibromas (NF), yet spatiotemporal and stage-specific cell state transitions and oncogenic networks driving benign-to-malignant transformation in MPNST remain elusive. In this study, we perform single-cell longitudinal analyses for early and advanced tumors and define the stage-specific kinetics of transcriptomics, cellular heterogeneity, and tumor cell fate decisions in murine and human MPNSTs. Our multistage and multilocation analyses of murine models, as well as benign NF and MPNST patient samples define the molecular events and cellular heterogeneity dynamics during NF-to-MPNST transition, highlighting differences and similarities of mouse and human tumors. Our studies provide a resource to uncover a cellular architecture rewiring and temporal acquisition of cellular heterogeneity of tumor-initiating Schwann cells, and driver events for promoting malignant transformation, pointing to potential therapeutic targets in MPNSTs. This is a collaboration between Dr. Jiyang Yu’s lab at St. Jude and Dr. Richard Lu’s lab at Cincinnati Children's Hospital Medical Center.
|Mouse MPNST||Jun 18, 2021|
|Mouse-Human MPNST integration||Jun 18, 2021|
|Human NF and MPNST||Jun 18, 2021|
|Human NF and MPNST tumor cell clusters (refined analysis)||Jun 18, 2021|