- Researchers have unveiled the progress they have made in creating a map of the cells in the human body.
- They say such a map could help diagnose and treat a variety of diseases.
- They compare the research to the Human Genome Project, which sequenced all the genes in the human genome.
Nearly 20 years ago, the decade-long
It was a groundbreaking achievement that has aided major advancements in biomedical technology and research.
This week, a potentially even more momentous achievement was introduced as the international Human Cell Atlas (HCA) consortium unveiled detailed maps of more than 1 million individual cells across 33 organs and systems.
The data, released in four major studies in the journal Science, represents the world’s most comprehensive, cross-tissue cell atlases. It’s a major stepping stone toward the HCA’s goal of mapping all of the cell types of the human body.
“The Human Cell Atlas is transforming our understanding of biology and disease,” said Sten Linnarsson, Ph.D., a professor at the Karolinska Institutet in Sweden and a member of the HCA Organizing Committee. “These cross-tissue studies represent a milestone for the HCA and single-cell biology by enabling systematic, in-depth comparison of the same cell types across development and adulthood. They are a great step forward to generating a Human Cell Atlas of all cell types in the human body, laying a foundation for a new era of diagnosis, healthcare, and precision medicine.”
At an online press conference, Sarah A. Teichmann, Ph.D., co-founder and principal leader of the HCA international consortium and head of cellular genetics at the Wellcome Sanger Institute in Cambridge, England, likened the project goal to creating “a Google map of the human body — a ‘Street View’ map of all cells and tissues.”
“What [the HCA] really opens up is the ability to understand tissue in all of its glory,” added Aviv Regev, Ph.D., a project co-founder and head of Genentech Research and Early Development.
The findings — and those that promise to follow — will aid researchers’ understanding of diseases, vaccine development, and areas such as anti-tumor immunology and regenerative medicine, experts said.
For example, said Teichmann, the research has already revealed “how immune cells develop in new and unexpected ways” — in the gut, the thymus gland, and other tissues, not just in bone marrow.
Regev said cell mapping “helps us understand precisely where disease arises” at the cellular level.
“People often think of the genome as a blueprint, but it’s really a parts list,” Stephen Quake, Ph.D., a founder of the Quake Lab, a biological research center at Stanford University in California, told Healthline.
Aided by machine learning, HCA researchers’ ability to separate tissue into single cells for analysis provides insight into how these genetic “parts” work together throughout the body.
“The genome is the parts list, but it’s not the operator — that’s the cells,” added Regev. “Once you have the genes, you have to understand where they operate.”
Regev likened the HCA project to “the Human Genome Project, but made for the 21st century.”
“The HCA is a completely open process, with more than 2,000 scientists in 83 countries,” she said. “That was not possible in the 1990s.”
Cell mapping will be particularly valuable for drug development, gene therapy, and cellular therapy, experts said.
“If you’re targeting a particular cell, you want to know where else in the body that cell is expressed,” Quake said.
“Knowing where else your target is expressed is crucial for preventing toxicity,” added Regev.
In one of the four initial studies, researchers from the Wellcome Sanger Institute sequenced RNA from 330,000 single immune cells to improve understanding of how immune cells function in different tissues.
“By comparing particular immune cells in multiple tissues from the same donors we identified different ‘flavors’ of memory T [immune] cells in different areas of the body, which could have great implications in managing infections,” said Teichmann. “Our openly available data will contribute to the Human Cell Atlas and could serve as a framework for designing vaccines, or to improve the design of immune therapies to attack cancers.”
In a second study, a Sanger Institute-led research team created a comprehensive atlas of the developing human immune system. The study included tissues involved in the formation of blood and immune cells and revealed that certain cell types are lost as humans age. Researchers said the findings can bolster in-vitro cell engineering and regenerative medicine research.
Regev led a third study that used machine learning algorithms to analyze frozen cellular material, overcoming a significant barrier in a research field that typically has to rely on fresh tissue for analysis. The 200,000 cells added to the atlas by the Broad Institute team were successfully associated with 6,000 single-gene diseases and 2,000 complex genetic diseases.
Regev said the study “opens the way to studies of tissues from entire patient cohorts at the single-cell level.”
“We were able to create a new roadmap for multiple diseases, by directly relating cells to human disease biology and disease-risk genes across tissues,” she said.
Finally, a study by Quake and colleagues at the Chan Zuckerberg Biohub used single-cell RNA sequencing of live cells to analyze multiple organs from one donor.
That enabled comparisons of different tissues while controlling for factors such as genetic background, age, and environmental effects.
The resulting cell atlas, which encompasses more than 400 cell types, was dubbed “The Tabula Sapiens.”
“The Tabula Sapiens is a reference atlas that provides a molecular definition of hundreds of cell types across 24 organs in the human body,” said Quake.
The findings revealed new insights into cellular biology, including how the same gene can be spliced differently into various cell types and how clones of immune cells can be shared across tissues.