The application of mass cytometry to developmental biology has revolutionized our understanding of cellular dynamics during embryogenesis and organ development. This chapter builds upon the concepts introduced in earlier sections, particularly Chapter 28 on Reproductive Medicine and Fetal Development, to explore how mass cytometry is unveiling the intricate processes of cellular differentiation and lineage specification.
Mapping Cellular Trajectories During Embryogenesis
Mass cytometry’s ability to simultaneously measure dozens of cellular markers has enabled researchers to track cellular trajectories with unprecedented resolution during embryonic development. Setty et al. (2016) introduced Wishbone, a computational method that identifies bifurcating developmental trajectories from single-cell data. This algorithm, when applied to mass cytometry data, has allowed for the detailed mapping of cell fate decisions during early embryogenesis (Setty et al., 2016, Nature Biotechnology, 34(6), 637-645).
Building on this foundation, a recent study by Mittnenzweig et al. (2021) published in Nature, “A single-embryo, single-cell time-resolved model for mouse gastrulation,” used a combination of flow cytometry and spatial transcriptomics to create a comprehensive atlas of mouse embryo development. This work provided unprecedented insights into the spatial and temporal dynamics of cellular differentiation during early embryogenesis.
Breast Organoids: A Window into Normal Mammary Biology and Cancer Risk
Building on the application of mass cytometry in developmental biology, a study showcases its power in unraveling the complexities of adult tissue maintenance and cancer risk. Rosenbluth et al. (2020) in Nature Communications have developed a breakthrough organoid culture system for normal human breast tissue that preserves the intricate cellular architecture and differentiation patterns of the mammary gland. Using mass cytometry, they demonstrate that these organoids maintain the protein expression profiles of their tissue of origin with remarkable fidelity, including rare cell populations often lost in traditional cultures. This system allows for long-term study of normal breast biology and early cancer development, particularly in high-risk individuals such as BRCA1 mutation carriers. By manipulating growth conditions, researchers can alter the balance of cell types, providing a powerful tool for understanding lineage specification in the adult mammary gland. This work represents a significant advance in applying mass cytometry beyond embryonic development to adult tissue dynamics and cancer risk, offering a vital bridge between animal models and human studies in breast biology.
By leveraging the high-dimensional capabilities of mass cytometry, researchers are continually uncovering new layers of complexity in developmental processes. From mapping the earliest stages of embryogenesis to understanding the fine-tuned mechanisms of cellular differentiation, mass cytometry is helping to write a more detailed story of how complex organisms emerge from a single cell. As this field continues to evolve, it promises not only to deepen our understanding of developmental biology but also to inform strategies for regenerative medicine and the treatment of developmental disorders.
Organoids are revolutionizing drug testing, potentially reducing animal experiments. Companies like Cellesce and DefiniGEN are at the forefront of this technology. Testing drugs on organoids can provide more human-relevant results and help streamline the drug development process, potentially bringing treatments to patients faster. Anecdote: Researchers at the Hubrecht Institute created a 'mini-gut' organoid that survived for more than 5 years! As reported in Nature (Sato et al., 2011), "These organoids have been continuously cultured for >1.5 years and maintain all hallmarks of the original epithelium." It's like having a tiny, immortal version of your intestine in a dish!
