横纹肌肉瘤
祖细胞
生物
细胞
转录组
间充质干细胞
细胞培养
干细胞
细胞分化
细胞融合
癌症研究
细胞生物学
遗传学
病理
医学
基因表达
基因
肉瘤
作者
Sara G. Danielli,Yun Wei,Michael A. Dyer,Elizabeth Stewart,Heather Tillman,Marco Wachtel,Beat W. Schäfer,Anand G. Patel,David M. Langenau
标识
DOI:10.1038/s41467-024-50527-2
摘要
Abstract Rhabdomyosarcoma (RMS) is a pediatric tumor that resembles undifferentiated muscle cells; yet the extent to which cell state heterogeneity is shared with human development has not been described. Using single-cell/nucleus RNA sequencing from patient tumors, patient-derived xenografts, primary in vitro cultures, and cell lines, we identify four dominant muscle-lineage cell states: progenitor, proliferative, differentiated, and ground cells. We stratify these RMS cells/nuclei along the continuum of human muscle development and show that they share expression patterns with fetal/embryonal myogenic precursors rather than postnatal satellite cells. Fusion-negative RMS (FN-RMS) have a discrete stem cell hierarchy that recapitulates fetal muscle development and contain therapy-resistant FN-RMS progenitors that share transcriptomic similarity with bipotent skeletal mesenchymal cells. Fusion-positive RMS have tumor-acquired cells states, including a neuronal cell state, that are not found in myogenic development. This work identifies previously underappreciated cell state heterogeneity including unique treatment-resistant and tumor-acquired cell states that differ across RMS subtypes.
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