Tabula Sapiens 2.0 assembled an atlas of 1,1 million cells from 28 human tissues
Tabula Sapiens 2.0 assembled an atlas of 1,1 million cells from 28 human tissues
On September 2, Cell published a paper describing the second version of Tabula Sapiens. The researchers added nine donors and four tissues and examined the RNA profiles of cells showing signs of cell cycle arrest.
RNA molecules are working copies of genes. They indicate which genes a cell is reading at a given time. Comparisons across organs can easily conflate tissue characteristics with differences among individuals and differences in sample processing. The researchers therefore collected multiple organs from four of the nine new donors. Comparing tissues from the same person allowed them to separate the contribution of tissue more clearly from some of the variation associated with the donor.
To analyze senescence, a stable form of cell cycle arrest, the authors defined an operational criterion. A cell had to contain an RNA copy of CDKN2A, a gene associated with cell cycle arrest, and no RNA copy of MKI67, a marker of active cell division. This criterion identified 48 114 cells from 25 tissues and 21 donors. For each combination of cell type, tissue, and donor, the researchers compared the RNA profiles of these cells with those of the other cells in the same group.
In this set, they identified 3 792 genes with increased RNA levels. After CDKN2A, the most widespread was CDKN2B, which is also associated with cell cycle arrest. Its RNA level was elevated in 18 of 30 broad cell groups. CXCL8 and MIF were elevated in five such groups, while SERPINE1 was elevated in two.
The authors then organized these genes into 17 programs, defined as groups of genes whose RNA levels change together. Programs related to cell adhesion were more prominent in epithelial cells, which form the coverings and linings of organs, and in fibroblasts, which provide structural support to tissues. Programs related to energy metabolism and to the systems that assemble and break down proteins changed in different ways across immune, epithelial, and stem cells.
The operational criterion produced a shared cell set, while its RNA programs varied primarily with cell type.