Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Nat Commun. 2021 Mar 1;12(1):1366. doi: 10.1038/s41467-021-21650-1.
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.
癌症干细胞驱动多种癌症的疾病进展和复发。尽管如此，对这些细胞的全面描述仍然难以捉摸，因此无法从源头彻底消灭癌症。在急性髓细胞白血病 (AML) 中，白血病干细胞 (LSC) 是导致死亡率的根源，但由于其丰度低且与健康造血干细胞 (HSC) 高度相似，因此难以分离。在这里，我们证明通过结合单细胞转录组学和使用核和线粒体体细胞变体进行谱系追踪，可以识别和分子分析 LSC、HSC 和前白血病干细胞。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体。我们的方法能够识别 LSC 特异性基因表达程序，并描述白血病突变诱导的分化障碍。总之，我们展示了单细胞多组学方法在表征癌症干细胞方面的强大功能。
