Single‐cell Transcriptomics Uncovers Cellular Architecture and Developmental Trajectories in Hepatoblastoma
Single‐cell Transcriptomics Uncovers Cellular Architecture and Developmental Trajectories in Hepatoblastoma
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DOI：
10.1002/hep.32775
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Qiang Xia
中科院分区：
文献类型：
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作者：
Hongting Huang;Liang Wu;Li Lu;ZiJie Zhang;Bijun Qiu;Jialin Mo;Yi Luo;Zhifeng Xi;Mingxuan Feng;Ping Wan;Jianjun Zhu;Dingye Yu;Wei Wu;Kezhe Tan;Jiangbin Liu;Qingfeng Sheng;Ting Xu;Jinyan Huang;Zhibao Lv;Yujie Tang;Qiang Xia
Hepatoblastoma(HB) is the predominant type of childhood liver cancer. Treatment options for the clinically advanced HB remain limited. We aimed to dissect the cellular and molecular basis underlying HB oncogenesis and heterogeneity at the single-cell level, which could facilitate a better understanding of HB at both the biological and clinical levels.Single-cell transcriptome profiling of tumor and paired distal liver tissue samples from five patients with HB was performed. Deconvolution analysis was used for integrating the single-cell transcriptomic profiles with the bulk transcriptomes of our HB cohort of post-neoadjuvant-chemotherapy tumor samples. A single-cell transcriptomic landscape of early human liver parenchymal development was established for exploring the cellular root and hierarchy of HB oncogenesis. As a result, seven distinct tumor cell subpopulations were annotated, and an effective HB subtyping method was established based on their compositions. A HB tumor cell hierarchy was further revealed to not only fit with the classical cancer stem cell(CSC) model but also mirror the early human liver parenchymal development. Moreover, FACT inhibition, which could disrupt the oncogenic positive feedback loop between MYC and SSRP1 in HB, was identified as a promising epigenetic-targeted therapeutic strategy against the CSC-like HB1-Pro-like1 subpopulation and its related high-risk Pro-like1 subtype of HB.Our findings illustrate the cellular architecture and developmental trajectories of HB via integrative bulk and single-cell transcriptome analyses, thus establishing a resourceful framework for the development of targeted diagnostics and therapeutics in the future.
