Chapter 20: Cancer Stem Cells and Cellular Hierarchies

In the intricate world of cancer biology, cancer stem cells (CSCs) stand as enigmatic maestros, orchestrating the complex symphony of tumor growth and progression. Mass cytometry has emerged as a powerful tool to unveil these elusive conductors and map the cellular hierarchies they command. Let’s embark on a journey through this fascinating realm, where cutting-edge technology meets one of cancer’s most perplexing mysteries.

Identification of Cancer Stem Cell Populations

The hunt for cancer stem cells has been likened to searching for a needle in a haystack – if that needle could shape-shift and the haystack was constantly changing. Mass cytometry, with its ability to analyze dozens of parameters simultaneously at the single-cell level, has brought unprecedented clarity to this search.

A landmark study by Gonzalez et al. (2018) published in Cell Reports used single-cell mass cytometry to identify commonly occurring cell subsets in high-grade serous ovarian tumors. This work revealed distinct cell populations with stem-like properties, providing a high-resolution map of cellular heterogeneity in ovarian cancer.

Lineage Tracing in Tumor Development

Tracing the lineage of cells in tumor development is akin to reconstructing a family tree where some members can spontaneously change their identities. Mass cytometry has provided invaluable tools for this complex task.

A fascinating study by Yang et al. (2022) in Cell, “Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution,” identified the subclonal dynamics of tumors, gene modules underlying expansion, transient increases in cellular plasticity, stereotypical evolutionary paths to aggressiveness across tumor genotypes, and the spatial and phylogenetic origins of metastases by using single-cell RNA sequencing.

Lineage tracing in tumor development

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Diving into cancer stem cells was like trying to find a needle in a haystack - if the needle could shape-shift and the haystack was constantly moving. Mass cytometry becomes your metal detector in this cellular treasure hunt. You can spent countless nights staring at plots, convinced yourself you've found the Holy Grail of cancer biology, only to realize it was just another cellular dead end.

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