Researchers have created an atlas, named Tabular Sapiens, for over 400 distinct cell types in humans.
Published in Science, the data enable new insights into how the human genome parts list is used to create distinct cell types within the human organism.
In addition, the atlas reveals many other aspects of human biology. From how the same gene can be spliced differently in different cell types, to how shared cell types in different tissues can have subtle differences in their identities. The atlas also provides insight into how clones of the immune system can be shared across tissues.
The Tabular Sapiens Consortium, who created the atlas, say “[it] represents a broadly useful reference to deeply understand and explore human biology at cellular resolution”.
Creating a cell atlas
The issue with current approaches to make cell atlases, is that individual organs are often collected at different locations, from different donors, and processed using different protocols. Controlled comparisons of cell types between different tissues and organs are especially difficult. Donors may differ in genetic background, age, environmental exposure, and epigenetic effects.
To address this, the Tabular Sapiens Consortium developed an approach to analysing large numbers of organs from the same individual.
The consortium collected multiple tissues from individual human donors. Nearly 500,000 cells from 24 tissues and organs of 15 normal human subjects were analysed. Then, they performed coordinated single-cell transcriptome analyses on live cells. Working with live cells, as opposed to isolated nuclei, ensured that the dataset includes all messenger RNA transcripts within the cell.
The authors note, “molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs”.
The full dataset can be explored online with the cellxgene tool.
Tabular Sapiens – enabling molecular characterisation
The Tabula Sapiens has revealed discoveries relating to shared behaviour and subtle, organ-specific differences across cell types.
T cell clones were found to be shared between organs and characterised organ-dependent hypermutation rates among B cells. Similarly, endothelial cells and macrophages are shared across tissues, often showing subtle but clear differences in gene expression.
The Tabula Sapiens also provided an opportunity to densely and directly sample the human microbiome throughout the gastrointestinal tract. The intestinal microbiome was revealed to have nonuniform species distributions down to the 3-inch (7.62-cm) length scale.
Finally, the consortium found an unexpectedly large and diverse amount of cell type–specific RNA splice variant usage. They discovered and validated many previously undefined splices.
The authors write, “the Tabula Sapiens is part of a growing set of data that, when analysed together, will enable many interesting comparisons of both a biological and technical nature.”
Written by Poppy Jayne Morgan
Image Credit: Canva
