Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma.

ABSTRACT: Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subc

SUBMITTER: Roehrig A 

PROVIDER: S-EPMC11001886 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature