Chan Zuckerberg Initiative (HCA)

Over the past two decades, researchers have made extensive efforts to define the body from the inside out through various large-scale, international ventures, such as the Human Genome Project, the Human Epigenome Project, and the Human Proteome Project.

Now, research groups around the world are working on a new reference guide that will add unprecedented insight into cells’ roles in health and disease. The Human Cell Atlas (HCA) will outline the body’s incredible variety of cells and map how each of them relates to one another and communicates in 3D space.

Recently, the Chan Zuckerberg Initiative (CZI)— established by Facebook founder Mark Zuckerberg and his wife, Priscilla Chan, AB ’07—awarded nearly $8 million in grants to support the work of three researchers in the Blavatnik Institute at Harvard Medical School who are engaged in HCA projects: Jonathan G. Seidman, AB ’72, PhD, the Henrietta B. and Frederick H. Bugher Foundation Professor of Genetics; Allon Klein, PhD, an associate professor of systems biology; and Peter Kharchenko, PhD ’05, the Gilbert S. Omenn, MD ’65 Associate Professor of Biomedical Informatics.

Using a grant of $4 million split among eight institutions in the U.S. and Europe, Seidman and his colleagues are investigating how RNA differs from cell to cell, using technology that traces each cell to its unique location. The team intends to build a reference atlas from healthy human hearts that could not be transplanted in patients. This information will eventually form the basis, Seidman says, for determining what processes might go wrong within these cellular populations in cardiac disease.

“Out of an adult human’s 37 trillion cells, the heart alone is about 5 billion,” Seidman says. “The prevailing view used to be that this structure was simply made of muscle and non-muscle cells, but now we know that the real picture is far more complicated.”

Klein, whose work centers on stem cells, will probe a system that is rich in cells continually differentiating into a variety of fates: bone marrow hematopoietic cells, which make up every component of blood.

“We can think of this in much the same way as having a very accurate map of continents or seas that allows ships to navigate new horizons,” Klein says. “If we want to understand the physiology of tissues or how they’re affected by disease, having a very detailed map of these tissues is an important prerequisite.”

Toward that end, he and his colleagues—across six labs at HMS and its affiliate hospitals—will use a $2 million grant to analyze bone marrow cells collected clinically, characterize different cell types by single-cell sequencing, and track changes in these cell populations over time.

With a $1.75 million grant split among three labs at HMS and its affiliates, Kharchenko and his team will investigate the spatial organization of lymph nodes using single-cell analysis and will also study how these cells interact.

“We can analyze gene expression to give us a detailed catalog of what kinds of cells are present in lymph nodes, which is very useful—it’s like having a list of actors in a play,” he says. “But what we can’t derive from this list is how they talk to each other.”

New techniques developed within HMS and beyond will provide insight into this communication, Kharchenko says. His own lab will use computational techniques and statistical models to interpret the generated data.

“We’re excited to support investigators at Harvard who are part of international, interdisciplinary collaborations that are accelerating progress toward a first draft of the Human Cell Atlas,” says CZI Science Program Officer Jonah Cool. “These networks of experts across scientific fields and time zones are demonstrating the advances in science that are possible when people pursue common goals.”

This article originally appeared in the spring 2020 issue of Pulse, the biannual newsletter of the Harvard Medical School Office of Alumni Affairs and Development, which celebrates the heart and impact of the HMS community