Chromatin and Gene Regulatory Dynamics of Optic Nerve Invasion in Retinoblastoma at Single-Cell Resolution

Abstract

AbstractRetinoblastoma is a rare and aggressive form of eye cancer that arises from the retina’s photoreceptor precursor cells. Yet, the mechanism of cancer evolution in optic invasion and the identification of molecularly defined tumor-propagating cells has not been reported. Using single-cell RNA and ATAC sequencing, we uncovered a propagating cell named STER after invasion of the optic nerve. We also report on the dynamic processes of photoreceptor degeneration and optic nerve injury in the retina and identify potential regulatory elements and transcription factors involved. STER cells mediate optic nerve destruction and retinal degeneration during the proliferation and migration of retinoblastoma. Finally, we develop drug sensitivity testing algorithms for malignant clusters, providing potential therapeutic targets and drug predictions for retinoblastoma invasion.