Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma

Jie Yang,Yanping Han,Yiyi Feng,Yongyun Li,Xiaofang Xu,Xiaoyu He,Min Zhou,Chunyan Zong,Renbing Jia,Jiayan Fan

doi:10.1038/s41419-021-04390-4

Abstract

Retinoblastoma is a childhood retinal tumour that is the most common primary malignant intraocular tumour. However, it has been challenging to identify the cell types associated with genetic complexity. Here, we performed single-cell RNA sequencing on 14,739 cells from two retinoblastoma samples to delineate the heterogeneity and the underlying mechanism of retinoblastoma progression. Using a multiresolution network-based analysis, we identified two major cell types in human retinoblastoma. Cell trajectory analysis yielded a total of 5 cell states organized into two main branches, and the cell cycle-associated cone precursors were the cells of origin of retinoblastoma that were required for initiating the differentiation and malignancy process of retinoblastoma. Tumour cells differentiation reprogramming trajectory analysis revealed that cell-type components of multiple tumour-related pathways and predominantly expressed UBE2C were associated with an activation state in the malignant progression of the tumour, providing a potential novel “switch gene” marker during early critical stages in human retinoblastoma development. Thus, our findings improve our current understanding of the mechanism of retinoblastoma progression and are potentially valuable in providing novel prognostic markers for retinoblastoma.

Highlights

Retinoblastoma is the most common ocular tumour of childhood and is fatal if left untreated
The patients were Notably, it was consistent with the results of pseudotime all diagnosed as group E advanced retinoblastoma with endo- trajectory analysis (Supplementary Fig. 4)
Enucleation was the primary that the cone precursor cells might develop into premalignant treatment without any other treatments

Summary

Introduction

Retinoblastoma is the most common ocular tumour of childhood and is fatal if left untreated. This malignancy is generally detected in infants or young children under the age of 3 years, and 7–10% of retinoblastomas are diagnosed at the neonatal stage during the first month of life and occasionally at birth [1]. Retinoblastoma is thought to result from the inactivation of the RB1 gene [4]. Studies suggest that biallelic RB1 inactivation leads to a non-proliferative retinoma, and progression to retinoblastoma requires additional genetic aberrations [5]. ~2% of retinoblastomas do not harbour RB1 alterations, and the presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features [6]

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