Are the Answers to Disease in Our Cells?

How Mapping Human Cells Can Transform Our Understanding of Health and Disease

To make advances in treating disease, we need a common reference map of all human cells: types, numbers, locations, relationships, and molecular components. The Human Cell Atlas aims to create a foundational resource with the power to transform our understanding of health and disease.

We’re proud to support this international effort by funding 38 collaborative, multidisciplinary science teams as part of the Seed Networks for the Human Cell Atlas. Over 200 grantees — physicians, experimental scientists, and computational scientists — will contribute data and tools towards a first draft of the Human Cell Atlas.

Learn about CZI’s Seed Networks grantees and the insights they’re gaining into what shapes our health:

An immunofluorescence image of the first part of the small intestine, called the duodenum. Photo provided by Emma Lundberg, KTH Royal Institute of Technology, Sweden.

Immunofluorescence microscopy is a technique where researchers thinly slice tissues and treat them with dyes to track the proteins that define unique features or processes present in a cell and can help diagnose diseases like cancer. A team of three researchers from Hungary, Denmark, and Sweden will use this method to study healthy and diseased human liver cells.

“These types of images will be the starting point for our project studying deep visual proteomics, or sets of proteins. I hope this work will take us one step closer to the next generation of pathology.” — Emma Lundberg, KTH Royal Institute of Technology, Sweden.

These brightly colored shapes are building blocks of respiratory tissues. Photo provided by Purushothama Rao Tata, Duke University School of Medicine, United States.

To develop the first cell map of the human lung, an international network of 16 researchers will study adult and pediatric tissue using single cell and spatial genomics, microscopy, anatomic, and computational methods.

“We aim to develop a cell atlas of the healthy adult lung that will serve as a roadmap for future studies focused on lung disease.” — Alexander Misharin, Northwestern University, United States.

Myelin from oligodendrocytes (orange cell, top) wraps around nerve cells (black cables) and allows rapid transmission of electric information in the nervous system. Certain oligodendrocyte precursor cells (light green “PacMan”) might contribute to diseases such as multiple sclerosis. Photo provided by Gonçalo Castelo-Branco, Karolinska Institutet, Sweden.

Oligodendrocyte cells produce myelin, a fatty material that protects nerve cells. The immune system destroys myelin in multiple sclerosis, a disease of the central nervous system that disrupts the flow of information within the brain and between the brain and body. Three researchers from Switzerland, Sweden, and the United Kingdom are working together to understand the characteristics of these important cells in samples from people of different regions, ages, and sexes.

“Our research will give new insights on the complexity of oligodendrocytes in the human brain and spinal cord. This might allow us to better understand their function in normal physiology, but also in several neurological pathologies, such as multiple sclerosis, leukodystrophies, and spinal cord injuries.” — Gonçalo Castelo-Branco, Karolinska Institutet, Sweden.

Different types of liver cells shown in different colors. Photo provided by Martin Guilliams, Ghent University, Belgium.

17 researchers across the world — from Singapore to Canada to Israel — will use computational tools to build a single cell map of the human liver.

“We are honored and excited to be joining forces with the best liver experts worldwide for this fantastic project using disruptive technologies to unravel the interactions between each of the individual building blocks that make a healthy human liver. This project will without any doubt change hepatology forever — the textbooks will have to be rewritten!” — Martin Guilliams, Ghent University, Belgium.

Left: An image of a single nuclei from a breast tumor. Right: Illustration of a breast duct in which malignant clones from a tumor are beginning to escape and invade the surrounding tissues. Photos provided by Nicholas Navin, The University of Texas MD Anderson Cancer Center, United States.

A group of six researchers from the University of California, Irvine; Cold Spring Harbor Laboratory; and The University of Texas MD Anderson Cancer Center are working together to study breast cancer. They plan to build a breast cell atlas that includes 100 women of multiple ages, breast sizes/densities, ethnicities, and body mass indexes to help ensure diversity when constructing the first draft of the Human Cell Atlas.

The Seed Networks is supporting two groups studying breast tissue; a different group of researchers will map the normal breast of ethnically diverse populations, including women of European, African, Latina, and Asian ancestry.

Caption: Human tendon cells (green) on engineered scaffolding (red) for tendon repair. Photo provided by Sarah Snelling, University of Oxford, United Kingdom.

Whether tendon problems affect the shoulder, knee, or ankle, they can cause almost constant pain. 11 researchers from the United Kingdom, Switzerland, and Denmark are part of the Tendon Seed Network to create a roadmap of what healthy tendons look like. This will help researchers assess current treatments and develop new ones.

“Our bioactive scaffolds allow tendon cells to grow and proliferate. Tendon cells respond to the chemistry and organization of these scaffolds, and we can use this response to design implantable scaffolds to successfully repair torn and diseased tendons.” — Sarah Snelling, University of Oxford, United Kingdom.

3D biomimetic matrices support the development of ovarian follicles (small, fluid-filled sacs in the ovary that release an egg to be fertilized during menstruation) both in vitro in a dish and after implantation back into the body. Photo provided by Ariella Shikanov, University of Michigan, United States.

A group of six researchers from three institutions is creating a cell atlas of the female reproductive system, including the ovaries, fallopian tube, and uterus.

“This work will transform our understanding of the intricacies of the female reproductive system and allow us to appreciate human physiology at an entirely new level.” — Erica Marsh, University of Michigan, United States.

Pictured here are models of human intestines that show fixed samples and live cell imaging of organoid development. Photos provided by Prisca Liberali, Friedrich Miescher Institute for Biomedical Research, Switzerland.

These stunning photos look like corals or deep-sea creatures. In fact, they’re models of human intestines. Scientists study these 3D models of cells — called organoids — to better understand how diseases affect our bodies’ organs and to develop effective treatments.

Researcher Prisca Liberali is part of a project with five other researchers to describe how multiple organs from a single individual develop over time.

A simulation of how muscle cells develop in mice. Video provided by Cole Trapnell, University of Washington, United States.

Three researchers working in Washington State and Missouri are using algorithms to study nine different types of tissue from 250 individuals to better understand how complex tissues form and function.

“We use advanced machine learning algorithms to reconstruct the unique histories and identities of single cells. These algorithms have helped us understand model systems, and further development will allow us to explore human genetic variation and provide explanations of how our tissues are built from different types of cells.” — Cole Trapnell, University of Washington, United States.

A normal fallopian tube epithelium (a type of tissue) stained to highlight cell membranes (red), nuclei (blue), and PAX8 genes (green). Photo provided by Ernst Lengyel, University of Chicago, United States.

“Identifying all cell types in the female pelvis will help us to find cures for intractable conditions such as ovarian cancer, endometriosis, and infertility.” — Ernst Lengyel, University of Chicago, United States.

Lengyel is leading a team of four researchers from the University of Chicago to characterize all cell types in the healthy female human reproductive system. They will also develop tools to analyze information from the data they gather.

Researchers identified a new immune cell in human blood that can help improve vaccination and cancer therapy. Image provided by Muzlifah Haniffa, Newcastle University, United Kingdom.

To study the effects of aging across the human lifespan, eight researchers working across the United Kingdom and the United States are mapping cellular diversity in the human immune system across multiple tissues and ages.

“Our atlas of immune populations in human organs will be an invaluable reference for disease, aging, and therapies that harness the immune system.” — Peter Sims, Columbia University, United States.

An immunofluorescence staining of breast epithelium tissue using two novel markers identified by single cell RNAseq (SLPI in red, NY-BR-1 in green), showing that these two cell types intermingle within the luminal epithelial compartment of lobular regions in the human breast. Photo provided by Kai Kessenbrock, University of California, Irvine, United States.

A team of researchers at the University of Irvine, California studying breast cancer conducted a pilot project funded by CZI where they profiled 200,000 breast tissue cells from 20 individuals. They documented over 12 cell types and 31 states. In a new Seed Networks project, the researchers plan to bring in additional interdisciplinary experts to expand this initial effort.

“Our recently published single cell-level census of the breast epithelium revealed two previously unrealized distinct cell types within the luminal compartment of the breast epithelium. The Human Breast Cell Atlas will allow us to identify previously unrealized cell types and lead to a better grasp of how cells communicate with each other in normal tissue homeostasis and disease.” — Kai Kessenbrock, University of California, Irvine, United States.

Spatial patterns of gene products (colored dots) in a tissue slice reveal differences between cells and how they interact with each other. In contrast to conventional technologies that examine cells in isolation, spatial technologies can tell us how cells function within their own tissue environment. Photo provided by Shyam Prabhakar, Genome Institute of Singapore, Singapore.

Researchers from Japan, Singapore, and South Korea are teaming up to build an atlas of Asian immune cell types and states across five major Asian population groups (Chinese, Japanese, Korean, Indian, and Malay). They will characterize variations such as those associated with ethnicity, environment, age, sex, and body mass index.

“Our network aims to characterize immune cell differences within and between Asian population groups, and thereby explain differences in physiology and disease.” — Shyam Prabhakar, Genome Institute of Singapore, Singapore.

Chan Zuckerberg Science Initiative

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Supporting the science and technology that will make it possible to cure, prevent, or manage all diseases by the end of the century.

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