In the single-cell and spatial analysis literature you will find hundreds of review articles on these technologies from the past year alone. Many of these reviews provide an overview of how single-cell and spatial technologies can turn an interesting research area into a potentially revolutionary real-world application.
Single-cell and spatial imaging technologies have enabled the characterisation of individual cells on a larger scale than ever before. This has facilitated the “mapping” of the human body at a cellular level using cell atlases.
The Human Cell Atlas
The Human Cell Atlas (HCA) is a large-scale collaborative project involving a team of international researchers. The HCA uses a combination of single-cell and spatial technologies to create cellular reference maps with the position, function and characteristics of every cell type in the human body. The cellular reference maps generated can be used to analyse the underlying molecular mechanisms of development and activity of different cell types and how cells interact to form tissues.
The objectives of the Human Cell Atlas are to:
- Catalogue all cell types and sub-types in the human body.
- Map cell types to their location within tissues to see the architecture of each tissue.
- Identify different cell states.
- Trace the developmental trajectories of cells.
- Reveal the cells and processes involved during development through to adulthood.
- Provide an openly available, globally representative resource, that will allow researchers worldwide to study and understand health and disease.
Other atlasing projects
Early cell atlas projects focused on the mouse, leading to the development of the Mouse Cell Atlas and the Tabula Muris. As well as the HCA, several tissue-specific human cell atlas efforts are ongoing. LungMAP and the Human Lung Cell Atlas aim to jointly produce a molecular atlas of the human lung throughout foetal development, as well as in paediatric and adult samples.
Profiling of the brain and the nervous system is led by the Cell Census Network BRAIN initiative. A focus on the immune system is also being led by the Immunological Genome Project (ImmgenH). All projects are utilising high-throughput scRNA-seq, with an increasing integration of spatial technologies.
Liquid biopsy and non-invasive diagnosis
Over the past decade, liquid biopsy has been explored – most commonly within cancer – and is based on the analysis of circulating biomarkers in blood. The promise of liquid biopsy is a minimally invasive blood test that can be used to diagnose and monitor disease with a high level of sensitivity and specificity. Within cancer, this would avoid the use of invasive tissue biopsy procedures, which are the current standard for diagnosis and result in a large amount of patient discomfort.
Single-cell liquid biopsy
Cells that are present in blood are already dissociated, making them easy to integrate into single-cell workflows. Within cancer, liquid biopsies typically target circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA). Both of these targets come with their own set of advantages and disadvantages (see Table 1).
Single-cell pathology and cancer diagnosis
Histological examination of tumour tissues is integral to diagnosing cancer and deciding treatment options. At present, this involves grading and staging based on tumour structure and cell morphology. Single-cell and spatial analysis technologies have emerged that are compatible with FFPE tissue, the most commonly used sample type within solid tumour histopathology and diagnosis.
This offers an opportunity for single-cell and spatial technologies to be applied to cancer diagnosis, potentially providing a method that can refine diagnosis and stratification to improve patient outcomes. This was illustrated in prostate cancer in a paper titled: Spatially resolved clonal copy number alterations in benign and malignant tissue, published in Nature in 2022.
Drug discovery and development
Determining drug properties such as activity, toxicity, and exposure is a complex process that is essential in the design of drug candidates and their advancement to the development stage. There are significant variations in the biological and physiological function of different cells which can affect their response to drugs. Single-cell analysis has been applied in drug discovery and development to help unravel the cellular processes underlying drug response and refine the drug development process.