Even in its early stages the Human Cell Atlas project is impacting the direction of research and development of RNA sequencing and other genetic tests

No one knows exactly how many cell types exist in the human body. Though traditional texts place numbers in the hundreds, recent studies have found ranges from thousands to tens of thousands. Anatomic pathologists and clinical laboratory scientists know that the discovery of new types of human cells could lead to the creation of new medical laboratory tests.

So, it’s an important development that leaders of the Human Cell Atlas Consortium, a project comparable to the Human Genome Project, have set out to determine the exact numbers of cell types. And their findings could open up an entirely new field of diagnostic testing for clinical laboratories and anatomic pathology and lead to advances in precision medicine.

With the ability to identify cell types and sub-types associated with human disease and health conditions, medical labs could have a useful new way to help physicians make diagnoses and select appropriate therapies.

Begun in 2016, the group’s mission according to the Human Cell Atlas website is “To create comprehensive reference maps of all human cells—the fundamental units of life—as a basis for both understanding human health and diagnosing, monitoring, and treating disease.”

The ambitious project aims to catalog every cell type in the human body and “account for and better understand every cell type and sub-type, and how they interact.”

Striving for Deeper Understanding of the Basics

Cells are the basic building blocks of life, but scientists don’t know exactly how many different types of cells there are.

In an NPR interview, Aviv Regev, PhD, Professor of Biology and a core member at the Broad Institute of MIT and Harvard, investigator at the Howard Hughes Medical Institute, and co-leader of the Human Cell Atlas Consortium, said, “No one really knows how many [cells types] there will be,” adding, “People guess anything from the thousands to the tens of thousands. I’m not guessing. I would rather actually get the measurements done and have a precise answer.”

In an innovative move, Regev and her team improved the method they were already using to sort cells—single-cell RNA sequencing. “All of sudden we moved from something that was very laborious—and we could do maybe a few dozen or a few hundred—to something where we could do many, many thousands in a 15- to 20-minute experiment,” she told NPR.

Dark Daily covered a similar advance in single-cell RNA sequencing in “‘Barcoding’ Cells in Nematodes Could Bring Advances and New Medical Laboratory Tools for Treatment of Cancer and Other Chronic Diseases.”

But the project is massive. A typical human body contains about 37.2 trillion cells. So, the Human Cell Atlas scientists decided to complete preliminary pilot projects to identify the most efficient and effective strategies for sampling and analyzing the various cells to create the full atlas.

“It’s kind of like we’re trying to find out what are all the different colors of Lego building blocks that we have in our bodies,” Sarah Teichmann, PhD, Head of Cellular Genetics and Senior Group Leader at Wellcome Sanger Institute in the UK, and co-leader of the Human Cell Atlas Consortium, told NPR. “We’re trying to find out how those building blocks—how those Lego parts—fit together in three dimensions within each tissue.”

Sarah Teichmann, PhD (left), and Aviv Regev, PhD (right), are co-leaders of the Human Cell Atlas Consortium, an ambitious project of MIT/Harvard Broad Institute that seeks to “create comprehensive reference maps of all human cells—the fundamental units of life—as a basis for both understanding human health and diagnosing, monitoring, and treating disease.” Such an advance could lead to significant advances in clinical laboratory and pathology testing and move healthcare closer to true precision medicine. (Photo copyrights: University of Cambridge and MIT/Broad Institute.

Some of the early pilot projects include a partnership with the Immunological Genome Project (ImmGen) to study and map the cells in the immune system. According to the Human Cell Atlas website, the partnership “will combine:

  • “deep knowledge of immunological lineages;
  • “clinical expertise and infrastructure needed to procure and process diverse samples;
  • “genomic and computational expertise to resolve the hundreds of finely differentiated cell types that compose all facets of the immune system; and,
  • the genomic signatures that define them.”

Other areas the pilot projects will address include:

Progress So Far

In the two short years since the Human Cell Atlas project began much work has already been accomplished, according to a news release. In addition to organizing the consortium and obtaining funding, the collaborators have published a white paper describing their goals and a framework for reaching them, as well as launching the pilot projects.

Such an ambitious project, however, is not without barriers and challenges. Regev and Teichmann, along with other collaborators, outlined some of those challenges in an article published in Nature.

The complexity of the human body combined with rapidly changing technology make simply agreeing on the scope of the project challenging. In order to meet that particular challenge, the collaborators plan to work in phases and drafts, which will allow for some flexibility and increasing focus on specifics as they go.

Other challenges include:

  • keeping the entire project open and fair;
  • procuring samples with consent and in an appropriate manner; and,
  • organizing in an efficient and effective manner.

The collaborators have developed and detailed strategies for meeting each of these challenges.

The Human Cell Atlas could impact treatments for every disease that affects humans and bring healthcare closer to accomplishing precision medicine goals. By knowing what cells exist in what parts of the human body—and how they typically behave at their most basic levels—the MIT/Harvard/Broad Institute scientists hope to understand what’s happening when those cells “misbehave” in expected ways. The knowledge garnered from the Human Cell Atlas is likely to be invaluable to anatomic pathologists and clinical laboratories.

—Dava Stewart

Related Information:

Ambitious ‘Human Cell Atlas’ Aims To Catalog Every Type of Cell in the Body

‘Barcoding’ Cells in Nematodes Could Bring Advances and New Medical Laboratory Tools for Treatment of Cancer and Other Chronic Diseases

International Human Cell Atlas Initiative

The Human Cell Atlas White Paper

A Revised Airway Epithelial Hierarchy Includes CFTR-Expressing Ionocytes

Single-Cell Transcriptomes from Human Kidneys Reveal the Cellular Identity of Renal Tumors

The Human Cell Atlas: from Vision to Reality

‘Barcoding’ Cells in Nematodes Could Bring Advances and New Medical Laboratory Tools for Treatment of Cancer and Other Chronic Diseases