Human Single-Cell Transcriptomic Atlas: Tabula Sapiens

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Summary

Researchers have meticulously crafted a comprehensive human reference atlas, the "Tabula Sapiens," by analyzing nearly 500,000 cells from 24 distinct tissues and organs, predominantly from a single donor. This atlas provides an unparalleled molecular insight into over 400 cell types, highlighting their distribution across various tissues and the unique gene expression within each tissue. Unlike previous methodologies that sourced organs from multiple donors, this study employed a unified approach, analyzing numerous organs from the same individual, ensuring consistency and eliminating variables like genetic background and age differences. The extensive dataset, accessible via the cellxgene tool, encompasses a vast array of cells, including immune, epithelial, endothelial, and stromal cells. Additionally, the research delved deep into the human microbiome, particularly within the gastrointestinal tract, revealing intricate species distributions. Among the myriad of discoveries, the atlas unveiled shared T cell clones across organs, organ-specific gene expression variations in endothelial cells and macrophages, and a plethora of cell type-specific RNA splice variants. This monumental work serves as a pivotal reference, offering profound insights into human biology at the cellular level.

Fig.1 Overview of human single cell transcriptomics atlas¹.

Research Criteria

They developed a detailed human map with around 500,000 cells from 24 varied body parts, often sourced from a single person. This map offered insights into over 400 distinct cell classifications and their placement in different tissues, alongside the variations in genetic expression. Represented donors spanned various ethnicities, were gender-balanced, averaged 51 in age, and had diverse medical histories.

Sample Type

They gathered information from a range of human organs and tissues, tallying 59 distinct samples. From this diverse collection, which spanned parts like the heart, skin, liver, and lungs, among others, they processed and examined each specimen. Out of this vast pool, 483,152 cells met the quality standards set.

Result—Data Collection and Display of Cell Types

Researchers undertook single-cell transcriptome analysis on tissues from 15 human donors, representing a diverse demographic. These donors varied in ethnicity, gender, age, and medical history. From these donors, a range of tissues were collected, with some donors contributing to a larger number of tissues. The study identified 475 distinct cell types with reference transcriptome profiles. The data, available on the Tabula Sapiens data portal, encompasses a vast array of organs and includes over 483,000 cells that passed quality control. The dataset is particularly rich, detailing 264,824 immune cells, 104,148 epithelial cells, 31,691 endothelial cells, and 82,478 stromal cells. To ensure accuracy, the transcriptome data was juxtaposed with conventional histologic analysis. Pathologists analyzed tissue sections, classifying cells into broad categories like epithelial, endothelial, immune, and stromal. The study found a general agreement between cell type proportions determined by single-cell sequencing and those identified through traditional methods, underscoring the reliability of the data.

Fig.2 Tabula Sapiens overview¹.

Result—Immune Cells Exhibit Tissue-Specific Gene Expression Variation as well as a Common Lineage History

In the Tabula Sapiens study, researchers delved into the gene expression and lineage histories of immune cells across various tissues. They discovered distinct gene expression patterns in macrophages from different tissues, with spleen macrophages notably expressing higher levels of CD5L, a lipid synthesis regulator. Additionally, epiregulin (EREG) expression was more pronounced in solid tissues like skin and uterus than in circulatory ones. The study also mapped T cell lineage relationships across tissues, revealing that many T cell clones are present in multiple organs. B cells in solid tissues exhibited a significantly higher mutational load than those in blood, suggesting a dominance of mature B cells in solid tissues. They developed an analysis which revealed differences in the prevalence of certain B cell-produced proteins, known as immunoglobulins, in various tissues. While blood samples had the fewest cells producing IgA, the large intestine showed a heightened presence of these cells. This pattern is consistent with the understood roles these proteins play in immune defense.

Fig.3 Analysis of immune and endothelial cell types found in many tissues¹.

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Reference

1. Tabula Sapiens Consortium*, et al. "The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans." Science 376.6594 (2022): eabl4896.