期刊
CELL DEATH & DISEASE
卷 12, 期 12, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41419-021-04390-4
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资金
- National Natural Science Foundation of China [81872339]
- Science and Technology Commission of Shanghai [20DZ2270800]
- Shanghai Science and Technology Development Funds [19QA1405100]
- Shanghai Ninth People's Hospital training programs [jyyq09201713]
- Young doctors' innovation team [QC201805]
This study utilized single-cell RNA sequencing to uncover the cellular heterogeneity and developmental mechanism of human retinoblastoma, identifying two major cell types and 5 different cell states. Cone precursors were found to be the initiating cells of retinoblastoma, while UBE2C was associated with an activation state in the malignant progression of the tumor.
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.
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