Deciphering normal and cancer stem cell niches by spatial transcriptomics: opportunities and challenges.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY Genes & development Pub Date : 2024-11-04 DOI:10.1101/gad.351956.124
Hirak Sarkar, Eunmi Lee, Sereno L Lopez-Darwin, Yibin Kang
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Abstract

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.

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通过空间转录组学解读正常和癌症干细胞龛位:机遇与挑战。
癌症干细胞(CSCs)通常表现出类似干细胞的特性,这取决于其生态位内错综复杂的促进干细胞生态系统。CSCs与其生态位之间的相互作用与肿瘤的异质性和抗药性有关。正常干细胞(NSCs)和CSCs具有相同的干性特征和共同的微环境成分,表现出显著的表型和功能可塑性。研究正常发育和肿瘤发生过程中不同器官的这些特性具有重要的研究意义和转化潜力。下一代测序(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纪元,为病变组织提供了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,因此可以研究特定龛位内的瘤内结构和细胞交叉对话。此外,通过多层次空间测序技术,还能发现缺氧、葡萄糖剥夺和其他微环境重塑等特定龛位特性的空间模式。在技术取得巨大进步的同时,计算工具的出现也缓解了特定技术的瓶颈。在这里,我们将讨论如何利用不同的空间技术来识别NSCs和CSCs及其相关的龛位。此外,通过对相关公共数据集的探索,我们回顾了目前在描述此类壁龛特征方面所面临的挑战(这些挑战往往受到技术限制的阻碍),以及用于解决这些问题的计算解决方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes & development
Genes & development 生物-发育生物学
CiteScore
17.50
自引率
1.90%
发文量
71
审稿时长
3-6 weeks
期刊介绍: Genes & Development is a research journal published in association with The Genetics Society. It publishes high-quality research papers in the areas of molecular biology, molecular genetics, and related fields. The journal features various research formats including Research papers, short Research Communications, and Resource/Methodology papers. Genes & Development has gained recognition and is considered as one of the Top Five Research Journals in the field of Molecular Biology and Genetics. It has an impressive Impact Factor of 12.89. The journal is ranked #2 among Developmental Biology research journals, #5 in Genetics and Heredity, and is among the Top 20 in Cell Biology (according to ISI Journal Citation Reports®, 2021).
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