Cancer stem cells (CSCs) often exhibit stem-like attributes that depend on an intricate stemness-promoting cellular ecosystem within their niche. The interplay between CSCs and their niche has been implicated in tumor heterogeneity and therapeutic resistance. Normal stem cells (NSCs) and CSCs share stemness features and common microenvironmental components, displaying significant phenotypic and functional plasticity. Investigating these properties across diverse organs during normal development and tumorigenesis is of paramount research interest and translational potential. Advancements in next-generation sequencing (NGS), single-cell transcriptomics, and spatial transcriptomics have ushered in a new era in cancer research, providing high-resolution and comprehensive molecular maps of diseased tissues. Various spatial technologies, with their unique ability to measure the location and molecular profile of a cell within tissue, have enabled studies on intratumoral architecture and cellular cross-talk within the specific niches. Moreover, delineation of spatial patterns for niche-specific properties such as hypoxia, glucose deprivation, and other microenvironmental remodeling are revealed through multilevel spatial sequencing. This tremendous progress in technology has also been paired with the advent of computational tools to mitigate technology-specific bottlenecks. Here we discuss how different spatial technologies are used to identify NSCs and CSCs, as well as their associated niches. Additionally, by exploring related public data sets, we review the current challenges in characterizing such niches, which are often hindered by technological limitations, and the computational solutions used to address them.

中文翻译：

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通过空间转录组学破译正常和癌症干细胞生态位：机遇与挑战


癌症干细胞 （CSC） 通常表现出类似干细胞的属性，这些属性依赖于其生态位内错综复杂的促进干细胞的细胞生态系统。CSCs 与其生态位之间的相互作用与肿瘤异质性和治疗耐药性有关。正常干细胞 （NSC） 和 CSCs 具有共同的干性特征和共同的微环境成分，表现出显着的表型和功能可塑性。在正常发育和肿瘤发生过程中研究不同器官的这些特性具有最重要的研究兴趣和转化潜力。新一代测序 （NGS）、单细胞转录组学和空间转录组学的进步开创了癌症研究的新时代，提供了病变组织的高分辨率和全面的分子图谱。各种空间技术具有测量组织内细胞位置和分子特征的独特能力，使对特定生态位内的肿瘤内结构和细胞串扰的研究成为可能。此外，通过多级空间测序揭示了生态位特异性特性（如缺氧、葡萄糖剥夺和其他微环境重塑）的空间模式的描绘。技术的巨大进步还与计算工具的出现相辅相成，以缓解特定于技术的瓶颈。在这里，我们讨论了如何使用不同的空间技术来识别 NSC 和 CSCs，以及它们的相关生态位。此外，通过探索相关的公共数据集，我们回顾了当前在描述此类利基市场方面面临的挑战，这些利基市场通常受到技术限制的阻碍，以及用于解决这些利基市场的计算解决方案。