Revealing Uncharted Biology with Single Cell Multiplex Proteomic Technologies: Platforms.
Understanding the intricate coordination of highly diverse cell types within healthy tissues and organs is essential for grasping their functionality. This coordination, often disrupted in disease, hinges on proteins-the primary drivers of cellular function. By examining protein abundance and activation states in single cells, researchers can identify key cell populations involved in both healthy and diseased states, including those influencing disease initiation, progression, and therapeutic responses. Single-cell multiplex proteomic platforms have recently emerged as powerful tools for biomedical research. Their strengths lie in revealing cell types that are rare or subtly different and would otherwise go undetected in bulk cellular analyses. This unique capability enables deeper insights into cellular behavior and disease mechanisms.
This book offers comprehensive overviews of technologies developed for multiplex single-cell proteomic analyses. It begins with the pioneering work from Professors Scott Tanner, Mitchell Winnick and Garry Nolan resulting in the development and early application of the mass cytometer, (CyTOF). The instrument merges flow cytometry with time-of-flight mass spectrometry and analyzes cells labelled with metal tagged antibodies. These components work together to enable CyTOF to perform highly multiplexed protein analysis at the single-cell level, offering a powerful tool for understanding complex cellular behaviors and interactions.
Recognizing that cellular organization is critical for tissue function, subsequent chapters explore advanced multiplex imaging platforms including Imaging Mass Cytometry (IMC), Multiplexed Ion Beam Imaging (MIBI), CODetection by InDExing, and Chip Cytometry. Later chapters present recent advances in these imaging platforms and data analysis approaches - Combined Nucleic Acid and Protein Quantification in situ, Tissue Schematics, and High-definition CODEX for 3D Multiplex Spatial Cell Phenotyping. These techniques integrate deep phenotyping with spatial mapping to provide unprecedented insights into cellular interactions within tissues. The book also highlights computational approaches essential for managing and interpreting the vast datasets generated by these technologies.
Revealing Uncharted Biology with Single Cell Multiplex Proteomic Technologies: Platforms help researchers in many fields, including developmental biology, cancer biology, immunology, neuroscience, and drug discovery gain an understanding about the theories and detailed methodologies behind these technologies. Integrating proteomics with genetic, epigenetic, and transcriptomic platforms, this book aims to inspire new research opportunities, ultimately advancing the development of reliable biomarkers and improving patient outcomes.
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Table of Contents
1. Personal and historical recollections of the early years of mass cytometry 2. Unveiling spatial biology of cellular landscapes with imaging mass cytometry 3. Single-Cell spatial phenotype mapping of tissue microenvironments with Multiplexed Ion Beam Imaging (MIBI) 4. Highly multiplexed spatial protein data using CODEX technology 5. Exploring uncharted spatial biology with ChipCytometry highly multiplexed imaging 6. Combined nucleic acid and protein quantification in situ 7. Tissue schematics 8. Highly-definition CODEX for 3D multiplex spatial cell phenotyping
Authors
Wendy Fantl Associate Professor (Research), Department of Urology, Stanford University, CA, USA.Wendy J. Fantl, PhD, is currently Head of Systems-level Translational Discovery Research in the Department of Discovery Sciences in Biomedical Research at Novartis. Wendy earned her Ph.D. in protein biochemistry from Rockefeller University and completed her postdoctoral studies at University of California, San Francisco focusing on receptor tyrosine kinase signal transduction. She spent over a decade at Chiron Corporation, where she applied her signaling expertise to targeting kinases. Subsequently, as Vice President of Cancer Biology at Nodality, she developed diagnostic phospho-flow tests for leukemias. In 2010, Wendy returned to academia and joined Stanford University, where her lab applied single cell multiplex proteomic technologies focusing on human high-grade serous ovarian cancer and clear cell renal carcinoma focusing on the tumor immune microenvironment and the DNA damage response. Wendy joined Novartis in 2022 to lead a team dedicated to using these technologies to further the mechanistic understanding of drug responses in patients, aligning with her commitment to patient care.
