Intratumoral heterogeneity, cell of origin and microenvironment in retinoblastoma [scRNA-seq]

Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. The diverse malignant and immune cells in tumors determine tumor progression, but the intratumoral heterogeneity, tumor microenvironment and their impact in RB remain poorly characterized. Here, we conducted transcriptomic profiles of around 70,000 cells from tumor samples of seven RB patients with pathological and clinical measurements. Fifteen cell types were identified where the majority were cone precursor-like (CP-like) and MKI67+ cone precursor (MKI67+ CP) cells. These cells expressed markers of cone precursor, suggesting that RB originated from cone precursor cells. The conversion of CP-like to MKI67+ CP led to the loss of photoreceptor function and increased cell proliferation ability in RB. By integrative copy number variation analysis, we found that two subtypes of MKI67+ CP cells were more malignant related to cell proliferation. The tumor microenvironment in RB was composed of three cell types, of which glial cells, including tumor-associated macrophages and astrocytes-like cells, created an immunosuppressive environment and promoted tumor growth and invasion by inhibiting the GALECTIN signaling pathway. Together, our study presents the first transcriptomic map of RB at a single-cell resolution and provides novel insights into the occurrence and progression of RB which will be important to the development of the future targeted therapy and immunotherapy. Single cells from seven independent retinoblastoma samples were captured in 10 batches (RB01, RB02, and RB03 samples repeated) using the 10X Chromium system.