ABSTRACT
Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.
Subject(s)
Cell Transformation, Neoplastic/metabolism , Neoplasms/metabolism , Tumor Microenvironment/physiology , Atlases as Topic , Cell Transformation, Neoplastic/pathology , Genomics/methods , Humans , Precision Medicine/methods , Single-Cell Analysis/methodsABSTRACT
Plant roots can regenerate after excision of their tip, including the stem cell niche. To determine which developmental program mediates such repair, we applied a combination of lineage tracing, single-cell RNA sequencing, and marker analysis to test different models of tissue reassembly. We show that multiple cell types can reconstitute stem cells, demonstrating the latent potential of untreated plant cells. The transcriptome of regenerating cells prior to stem cell activation resembles that of an embryonic root progenitor. Regeneration defects are more severe in embryonic than in adult root mutants. Furthermore, the signaling domains of the hormones auxin and cytokinin mirror their embryonic dynamics and manipulation of both hormones alters the position of new tissues and stem cell niche markers. Our findings suggest that plant root regeneration follows, on a larger scale, the developmental stages of embryonic patterning and is guided by spatial information provided by complementary hormone domains.
Subject(s)
Plant Roots/physiology , Cytokinins/metabolism , Gene Expression Profiling , Indoleacetic Acids/metabolism , Plant Cells , Plant Growth Regulators/metabolism , Plant Roots/cytology , Seeds , Single-Cell Analysis , Stem Cell Niche , Stem Cells/cytologyABSTRACT
The originally published version of this Research Highlight incorrectly stated that Guo-Cheng Yuan is at the University of California at Los Angeles; the correct affiliation is Dana-Farber Cancer Institute. The text has been corrected in the HTML and PDF versions of the paper.