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The function of Retinoblastoma tumor suppressor (pRB) is greatly influenced by the cellular context, therefore the consequences of pRB inactivation are cell-type-specific. Here we employ single cell RNA-sequencing (scRNA-seq) to profile the impact of an  Rbf  mutation during  Drosophila  eye development. First, we build a catalogue of 11,500 wild type eye disc cells containing major known cell types. We find a transcriptional switch occurring in differentiating photoreceptors at the time of axonogenesis. Next, we map a cell landscape of  Rbf  mutant and identify a mutant-specific cell population that shows intracellular acidification due to increase in glycolytic activity. Genetic experiments demonstrate that such metabolic changes, restricted to this unique  Rbf  mutant population, sensitize cells to apoptosis and define the pattern of cell death in  Rbf  mutant eye disc. Thus, these results illustrate how scRNA-seq can be applied to dissect mutant phenotypes.

Single cell RNA-sequencing identifies a metabolic aspect of apoptosis in Rbf mutant