Background: Cancer stem cells (CSCs) are biologically characterized by self-renewal, multi-directional differentiation and infinite proliferation, inducing anti-tumor drug resistance and metastasis. In the present study, we attempted to depict the baseline landscape of CSC-mediated biological properties, knowing that it is vital for tumor evolution, anti-tumor drug selection and drug resistance against fatal malignancy./nMethods: We performed single-cell RNA sequencing (scRNA-seq) analysis in 15208 cells from a pair of primary and metastatic sites of collecting duct renal cell carcinoma (CDRCC). Cell subpopulations were identified and characterized by t-SNE, RNA velocity, monocle and other computational methods. Statistical analysis of all single-cell sequencing data was performed in R and Python./nResults: A CSC population of 1068 cells was identified and characterized, showing excellent differentiation and self-renewal properties. These CSCs positioned as a center of the differentiation process and transformed into CDRCC primary and metastatic cells in spatial and temporal order, and played a pivotal role in promoting the bone destruction process with a positive feedback loop in the bone metastasis microenvironment. In addition, CSC-specific marker genes BIRC5, PTTG1, CENPF and CDKN3 were observed to be correlated with poor prognosis of CDRCC. Finally, we pinpointed that PARP, PIGF, HDAC2, and FGFR inhibitors for effectively targeting CSCs may be the potential therapeutic strategies for CDRCC./nConclusion: The results of the present study may shed new light on the identification of CSCs, and help further understand the mechanism underlying drug resistance, differentiation and metastasis in human CDRCC.

中文翻译：

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通过单细胞 RNA-seq 分析鉴定促进人类致命性肾细胞癌进展的新型癌症干细胞亚群

背景：癌症干细胞（CSCs）具有自我更新、多向分化和无限增殖的生物学特征，可诱导抗肿瘤耐药性和转移。在本研究中，我们试图描绘 CSC 介导的生物学特性的基线景观，知道它对肿瘤进化、抗肿瘤药物选择和对致命恶性肿瘤的耐药性至关重要。/n方法：我们对来自集合管肾细胞癌 (CDRCC) 的原发和转移部位的 15208 个细胞进行了单细胞 RNA 测序 (scRNA-seq) 分析。通过 t-SNE、RNA 速度、单片眼镜和其他计算方法鉴定和表征细胞亚群。所有单细胞测序数据的统计分析均在 R 和 Python 中进行。/n结果：鉴定并表征了 1068 个 CSC 细胞群，显示出优异的分化和自我更新特性。这些CSCs定位为分化过程的中心，按时空顺序转化为CDRCC原发细胞和转移细胞，在骨转移微环境中通过正反馈循环在促进骨破坏过程中发挥着举足轻重的作用。此外，观察到 CSC 特异性标记基因 BIRC5、PTTG1、CENPF 和 CDKN3 与 CDRCC 的不良预后相关。最后，我们指出有效靶向 CSC 的 PARP、PIGF、HDAC2 和 FGFR 抑制剂可能是 CDRCC 的潜在治疗策略。/n结论： 本研究的结果可能为 CSCs 的鉴定提供新的思路，并有助于进一步了解人类 CDRCC 的耐药、分化和转移的机制。