Whilst the intricate interplay among trillions of cells within the human body is what empowers us our capabilities, it is also one of the most perplexing challenges to unravel at times of health and diseases. The Human BioMolecular Atlas Program (HuBMAP), funded by the Common Fund at the National Institutes of Health, was launched in 2018 with the pivotal goal of constructing a comprehensive atlas of the human body at a single-cell level. This ambitious initiative aims to enable scientists to scrutinize the distribution of specific cell types within organ tissues and their corresponding profiles, translating all the single-cell data we obtain from advanced multi-omics methodologies into knowledge that facilitates an in-depth understanding of how the communication between these cells in the same microenvironment contributes to the underlying mechanisms of both normal organ function and any associated diseases.
Recently, Lake et. al presented a comprehensive spatially resolved single-cell atlas across the corticomedullary axis of the kidney featuring both healthy and injured cells by incorporating multimodal, high-dimensional data with existing knowledge from human and rodent models. They used multiomics assays to obtain the molecular and epigenetic landscape of each cell. Cells with similar profiles were then clustered together via unsupervised machine learning, revealing 100 distinct cell populations. A cross-disciplinary consortium was then brought together to identify cells with a consistent expression of known markers and annotate them in a standardized anatomical and cell type nomenclature. When characterizing cellular states that are associated with pathophysiological stress or injury, the team validated their findings by mapping their results onto an existing mouse of acute kidney injury to check for conserved cellular responses and molecular signatures to injury, such as an elevated expression of injury markers SPP1, CST3, CLU and IGFBP7in humans. These examples highlight the integration of extensive multi-omics data with our current knowledge base to create a functional 3D tissue map.
The spatially resolved atlas goes beyond identifying cellular subtypes and their molecular signatures. It can also offer insights about intercellular interactions through niche and ligand-receptor interaction analyses. Niche analysis revealed the diversity and proportions of cell type within a niche, while ligand-receptor analysis computed the probability of cell-cell communication between clusters. They also generated a heat map that visualizes pathway enrichment upon signals in the microenvironment to highlight significant contributors to ligand-receptor interactions. Therefore, the atlas becomes an openly available tool that can inform scientists of pathways and cell types involved in the transition from healthy to injured states, which could accelerate insights for predicting clinical outcomes, studying disease pathogenesis, and guiding targeted interventions.
Feature article: Lake, B.B., Menon, R., Winfree, S., Hu, Q., Ferreira, R.M., Kalhor, K., Barwinska, D., Otto, E.A., Ferkowicz, M., Diep, D., Plongthongkum, N., Knoten, A., Urata, S., Mariani, L.H., Naik, A.S., Eddy, S., Zhang, B., Wu, Y., Salamon, D. and Williams, J.C. (2023). An atlas of healthy and injured cell states and niches in the human kidney. Nature, [online] 619(7970), pp.585–594. doi:https://doi.org/10.1038/s41586-023-05769-3.