Human Tumor Atlas Network

A collection of research articles, methods and datasets from a collaborative initative tracking human tumor evolution in space and time

Cartoon depiction of tumor structures sculpted from tissue.

Credit: Jessica Johnson

Credit: Jessica Johnson

The Human Tumor Atlas Network leverages scientific collaboration to integrate samples, analytical modalities and tools into detailed atlases of tumor evolution. Expanding our spatial understanding of molecular, cellular and tissue features, HTAN offers a multidimensional view of cancer biology.

The video begins as a 3D volume of CODEX staining for epithelial cells (Pan-Cytokeratin, red), myoepithelial and fibroblasts (Smooth Muscle Actin, white), and immune cells (CD45, green) constructed from a 3D serial sectioning experiment on tissue block of a primary breast cancer sample. 3D volumes constructed from the Pan-Cytokeratin (red) and Smooth Muscle Actin (white) are then shown. Z-axis is to scale. (This video has no sound).

The video begins as a 3D volume of CODEX staining for epithelial cells (Pan-Cytokeratin, red), myoepithelial and fibroblasts (Smooth Muscle Actin, white), and immune cells (CD45, green) constructed from a 3D serial sectioning experiment on tissue block of a primary breast cancer sample. 3D volumes constructed from the Pan-Cytokeratin (red) and Smooth Muscle Actin (white) are then shown. Z-axis is to scale. (This video has no sound).

HTAN in numbers

Since 2018, the network of HTAN researchers has compiled multiomics data and applied novel analytical tools to expand our understanding of the complexity of tumor ecosystems across many organs and tumor types. The scope of the project exemplifies how to build a mosaic of understanding of cancer progression from spatial and molecular data. The tools and datasets generated provide a resource for the cancer research community to explore and discover new mechanisms of tumorigenesis.

Schematic of the scope and data of the HTAN project including number of tumor sites (21), atlases (14), cases (2,088), biospecimens (8,425), and analytical tools: 9 bulk omics methods, 3 single-cell omics, 10 imaging techniques, 8 spatial omics methods.

Dissecting tumor evolution

Multiplex immunofluorescence (CODEX) section from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

Tumor evolution and microenvironment interactions in 2D and 3D space

Molecular profiling approaches are key for providing insights into the biology and clinical behavior of cancer. However, such profiling approaches have typically been applied to dissociated cancer tissues without the spatial context of intercellular interactions within the tumor microenvironment. This study by Li Ding and colleagues provides a rich resource of spatially resolved genomic, transcriptomic and proteomic profiles across 131 tumor sections of various cancer types. As well as providing biological insights into the clonality and cellular organization of tumor subregions, this detailed and multilayered resource is ripe for future mining by the cancer community.

H&E section from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

Temporal recording of mammalian development and precancer

Lineage tracing methods based on CRISPR evolving barcodes are powerful for tracking the cellular histories of normal tissues and pathological ones such as cancer. In this study, Ken Lau and colleagues apply CRISPR lineage tracing to mouse development and mouse models of colorectal cancer. They identify timings and cell types underlying tissue-specific cell expansion during embryonic mouse development and during transitions to cancer. One notable finding is a polyclonal make-up of early cancers, with this clonal diversity becoming reduced during the transition to advanced cancers; this finding was recapitulated in human colorectal cancer samples from different stages of progression.

Spatial transcriptomics (Xenium, CosMx, Visium HD) section from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

Multi-omic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis

Snyder and colleagues chart the key genomic, cellular and molecular events underpinning the earliest steps in colorectal cancer formation with a comprehensive multiomic atlas of transcriptomic, proteomic, metabolomic, and lipidomic datasets from normal mucosal tissue, benign polyps, and dysplastic polyps. The atlas represents 93 samples from 6 patients with familial adenomatous polyposis.

Series of tumor histological slides depicting morphology staining and fluorescent molecular markers.

Multiplex immunofluorescence (CODEX), H&E, and spatial transcriptomics (Xenium, CosMx, Visium HD) sections from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

Multiplex immunofluorescence (CODEX) section from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

H&E section

Multiplex immunofluorescence (CODEX), H&E, and spatial transcriptomics (Xenium, CosMx, Visium HD) sections from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

H&E section from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

Spatial transcriptomics section

Multiplex immunofluorescence (CODEX), H&E, and spatial transcriptomics (Xenium, CosMx, Visium HD) sections from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

Spatial transcriptomics (Xenium, CosMx, Visium HD) section from a primary breast cancer sample with ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC).

Tools and methods

CODEX multiplex IF image of a primary breast cancer section with Pan-Cytokeratin (red), Smooth Muscle Actin (white), MKI67 (yellow), CD31 (cyan), CD3 (green), CD4 (magenta).

A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features

Single-nucleus and single-cell RNA sequencing plus spatial profiling (using four methods) of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis, and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

Quality control for single-cell analysis of high-plex tissue profiles using CyLinter

Artifacts from sample preparation to image acquisition and analysis, ranging from physical folds and debris to optical aberrations and image processing errors, can prevent single-cell analysis of multiplexed tissue imaging data. CyLinter helps remove these artifacts to improve biological interpretation of these data.

Multi-marker immunofluorescent staining of breast cancer tissue.

CODEX multiplex IF image of a primary breast cancer section with Pan-Cytokeratin (red), Smooth Muscle Actin (white), MKI67 (yellow), CD31 (cyan), CD3 (green), CD4 (magenta).

CODEX multiplex IF image of a primary breast cancer section with Pan-Cytokeratin (red), Smooth Muscle Actin (white), MKI67 (yellow), CD31 (cyan), CD3 (green), CD4 (magenta).

Browse the collection

Cartoon depiction of tumor structures sculpted from tissue.

View the HTAN collection page which includes all research articles, an editorial, feature article and Research Briefing.

Register here to join a webinar with HTAN leaders Li Ding, Ken Lau and Shannon Hughes. Hear insights into the background, strategies and latest exciting research findings from the HTAN consortium. Contribute to the discussion and have your questions answered live by the presenters.

Springer Nature © 2024 Springer Nature Limited. All rights reserved.