Human Single-Cell Transcriptome CellAtlas

Our understanding of how individual cells form distinct tissues and organs, and how each cell interacts with one another — is incomplete. Recent single-cell RNA sequencing (scRNAseq) analyses have described the landscapes of individual cell-types, along with their abundance and interactions, in homeostasis and during disease states, but these studies are often limited to a single organ. A systematic comparison of cell-types, across different tissues, is needed to understand shared and variable transcriptional features and how these specializations are important for organ function.

The [three attached articles, plus editorial] report the pan-tissue single-cell transcriptome atlases — covering more than a million cells, including 500 cell-types, across more than 30 human tissues from 68 donors. These two attached articles apply rigorous ontologies to consistently annotate and compare single cells between organs.

Interrogation of these large datasets reveals tissue-agnostic (i.e., antineoplastic drugs that treat cancers based on the mutations that they display, instead of the tissue type in which they appear) and tissue-specific cell features, identifies rare cell-types, and provides insights into cell-states that are likely to underlie disease pathogenesis (see the figure in the editorial, 3rd attachment from left). The Tabula Sapiens Consortium created a human reference atlas across 24 different tissues and organs — using scRNA-seq, leading to the characterization of more than 400 cell-types spanning epithelial, endothelial, stromal, and immune-cell compartments.

Eraslan et al. (1st attachment from left) took a complementary approach by applying single-nucleus RNA sequencing (snRNA-seq) to eight human tissue-types and profiled neuronal cells, muscle cells, and adipocytes (the latter which is very difficult to dissociate and capture using scRNA-seq). These cross-tissue approaches recapitulated conserved cell-type features and revealed cell-state adaptations to distinct tissue environments.

Conde et al., (2nd attachment from left) present an immune-cell atlas of myeloid and lymphoid lineages across adult human tissues. They developed CellTypist for automated immune-cell annotation and performed an in-depth dissection of cell populations, identifying 101 cell types or states from more than one million cells, including previously underappreciated cell states. These incredible summary papers represent a MAJOR breakthrough in single-cell identification opening all kinds of imaginable experiments that can now be proposed…!! 😊


Science, 13 May 2022; 376: 712, 713, & editorial pp 695-696

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