Cancer stem cells drive disease progression and relapse in many types of cancer. Despite this, a thorough characterization of these cells remains elusive and with it the ability to eradicate cancer at its source. In acute myeloid leukemia (AML), leukemic stem cells (LSCs) underlie mortality but are difficult to isolate due to their low abundance and high similarity to healthy hematopoietic stem cells (HSCs). Here, we demonstrate that LSCs, HSCs, and pre-leukemic stem cells can be identified and molecularly profiled by combining single-cell transcriptomics with lineage tracing using both nuclear and mitochondrial somatic variants. While mutational status discriminates between healthy and cancerous cells, gene expression distinguishes stem cells and progenitor cell populations. Our approach enables the identification of LSC-specific gene expression programs and the characterization of differentiation blocks induced by leukemic mutations. Taken together, we demonstrate the power of single-cell multi-omic approaches in characterizing cancer stem cells.

中文翻译：

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通过单细胞转录组学的克隆追踪鉴定白血病和白血病前干细胞

癌症干细胞在许多类型的癌症中驱动疾病进展和复发。尽管如此，这些细胞的全面表征仍然难以捉摸，并具有从源头上消灭癌症的能力。在急性髓细胞性白血病（AML）中，白血病干细胞（LSC）是死亡率的基础，但由于其丰度低且与健康的造血干细胞（HSC）具有高度相似性而难以分离。在这里，我们证明可以通过将单细胞转录组学与沿袭追踪相结合，同时使用核和线粒体体细胞变异体来鉴定LSC，HSC和白血病前干细胞并进行分子谱分析。虽然突变状态可以区分健康细胞和癌细胞，但基因表达可以区分干细胞和祖细胞群。我们的方法能够鉴定LSC特异性基因表达程序，并鉴定白血病突变诱导的分化区。综上所述，我们证明了单细胞多组学方法在表征癌症干细胞方面的功能。