Technologies and Methodologies of the Human Cell Atlas (HCA)

The Human Cell Atlas (HCA) is a comprehensive atlas of all human cells built on cutting-edge technologies and methods. These advanced technologies and methods provide the foundation for characterizing cellular diversity, states, and interactions at an unprecedented scale and resolution.

1. Single-cell sequencing

(1) Single-cell RNA sequencing (scRNA-seq): Mainly used to analyze gene expression in individual cells to identify cell types and states. Technologies such as Smart-seq and 10x Genomics are widely used.

(2) Single-cell ATAC-seq: Mainly used to map chromatin accessibility to gain insight into regulatory elements and gene activation mechanisms.

(3) Single-cell multi-omics: Mainly by integrating transcriptomics, proteomics, and epigenomics to provide a holistic view of cellular function.

2. Spatial transcriptomics

Technologies such as Visium and MERFISH preserve spatial context while analyzing gene expression, allowing researchers to understand cell localization and interactions within tissues.

3. Proteomics and epigenomics

(1) Mass spectrometry: mainly used to quantify proteins and post-translational modifications at the cellular level.

(2) ChIP-seq and CUT&RUN: mainly analyze histone modifications and transcription factor binding, linking epigenetic regulation to cell identity.

4. Imaging technology

(1) Multiplexed imaging: technologies represented by CODEX and MIBI can visualize multiple protein markers in tissues.

(2) Super-resolution microscopy: This technology can provide nanoscale details of cellular structure and interactions.

5. Computational tools

(1) Machine learning: algorithms represented by Seurat and Scanpy can analyze large single-cell datasets and identify patterns and clusters.

(2) Ligand-receptor analysis: tools represented by CellPhoneDB can predict intercellular communication networks.

6. Microfluidics and organoids

Microfluidics platforms enable high-throughput single-cell manipulation, while organoids provide 3D models for tissue-specific studies.

Together, the combination of these approaches enables HCA to construct a comprehensive, multidimensional atlas of human cells, thereby advancing our understanding of biology and disease.

References

[1] The Human Cell Atlas (HCA) (https://www.humancellatlas.org/)

[2] Collection, Nature Portfolio 2024 (https://www.nature.com/collections/jccbbdahji)

[3] Sarah Aldridge and Sarah Teichmann, Nature Communications 2020 (https://doi.org/10.1038/s41467-020-18158-5)