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

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 sa...

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Autores principales:	Jie Yang, Yongyun Li, Yanping Han, Yiyi Feng, Min Zhou, Chunyan Zong, Xiaoyu He, Renbing Jia, Xiaofang Xu, Jiayan Fan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/ca268cafa8374d9fb79152b477c889bf
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spelling	oai:doaj.org-article:ca268cafa8374d9fb79152b477c889bf2021-11-28T12:04:32ZSingle-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma10.1038/s41419-021-04390-42041-4889https://doaj.org/article/ca268cafa8374d9fb79152b477c889bf2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04390-4https://doaj.org/toc/2041-4889Abstract 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.Jie YangYongyun LiYanping HanYiyi FengMin ZhouChunyan ZongXiaoyu HeRenbing JiaXiaofang XuJiayan FanNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Jie Yang Yongyun Li Yanping Han Yiyi Feng Min Zhou Chunyan Zong Xiaoyu He Renbing Jia Xiaofang Xu Jiayan Fan Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
description	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.
format	article
author	Jie Yang Yongyun Li Yanping Han Yiyi Feng Min Zhou Chunyan Zong Xiaoyu He Renbing Jia Xiaofang Xu Jiayan Fan
author_facet	Jie Yang Yongyun Li Yanping Han Yiyi Feng Min Zhou Chunyan Zong Xiaoyu He Renbing Jia Xiaofang Xu Jiayan Fan
author_sort	Jie Yang
title	Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
title_short	Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
title_full	Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
title_fullStr	Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
title_full_unstemmed	Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
title_sort	single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/ca268cafa8374d9fb79152b477c889bf
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Single-cell transcriptome profiling reveals intratumoural heterogeneity and malignant progression in retinoblastoma

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