Cells can be described as the ‘building blocks’ of life. They are the fundamental units that make up our bodies. And not just our bodies; almost all life on Earth is made up of cells – from single-celled bacteria to 37 trillion-celled humans.
The Human Cell Atlas (HCA), which began in 2016, is aiming to map out all of the hundreds of different types of cells in the human body. Previously, cells have been characterised by their shape, size, location or proteins. But the latest advances in single-cell sequencing technology means there is a new way. Researchers are able to quantify which genes are active inside individual cells, giving unprecedented, detailed insight into their functions within tissues and organs.
Hundreds of thousands of cells have already been analysed by researchers working on the project, and vast amounts of data have been generated. Already the project is uncovering new types of cells, with implications for both health and disease. Teams across the globe, coordinated by researchers at the Sanger Institute, the Broad Institute in the US, the Riken and Karolinska Institutes in Japan and Sweden aim to revolutionise our understanding of the human body. Billions of cells will be analysed in total – from different areas of the body, in different states, and reacting to different stimuli.
We spoke to Dr Kerstin Meyer, Principal Staff Scientist at the Sanger Institute, who is preparing to present Human Cell Atlas work to a global audience at AAAS in Seattle, about what it’s like to work on a such a huge, collaborative endeavour.
Impacts of the Human Cell Atlas
We started by talking about the future of the Human Cell Atlas. “For me, a really exciting thing about the HCA is the shift towards understanding disease,” says Kerstin. “The HCA started its life focussing on healthy cells, but our research is moving from the laboratory towards healthcare.”
“Earlier this year we published our study on asthma. It’s a disease that affects so many people, including children. Why is it that an asthmatic lung suddenly produces all this extra mucus? We found what we’ve called a muco-ciliated cell – there are either more of these cells in asthmatic lungs, or they seem to get stuck in a developmental transition. Just knowing that might help towards looking at how to get cells out of that stage, or how to target them more directly with asthma treatments.”
“Our work is currently describing how cells are different between health and disease. It doesn’t immediately translate into understanding the mechanisms of disease, but we need the information as a basis for that next step. We’re re-defining what we know about the human body in health and disease, at the cellular level.”
From gene to medicine
Kerstin discussed how the Human Cell Atlas is driving our understanding of how the genome works in the body, and how each of our cells is using the same set of DNA to undertake its own, very different tasks.
“It’s amazing to think we are describing where every gene is expressed in the human body. And we want to put that information to work. For example if you give a drug to inhibit a particular protein, you might have a good idea in which cells to expect side effects. If you have choices about how you deliver those drugs, and only target cells where that gene and protein are active, you might have a more effective medicine.”
“Over the last ten years, there have been massive efforts analysing the genetics that drive disease. From those studies, we often know which genes to look at in any particular disease, but the HCA work means we can now say in exactly which cell type and in which tissue these genes are active, or expressed,” she says.
“The next step for HCA is both an opportunity and a challenge - it is closer collaborations with clinicians. We want to integrate the huge amount of medical knowledge that is out there and combine it with our molecular description of single cell behaviour.”
The Human Cell Atlas is also investigating how cells behave in the very first moments of life. We all start out as one cell, which divides, many, many times, to become hundreds of different cell types, organised into layers, structures, tissues and organs. They eventually add up to the 37 trillion cells that make up an adult human.
“I think one of the most exciting things in our field is the ability to start to disentangle human development. People have studied mouse development to a great depth, but the truth is humans are different. We now see this for many different organs and therefore mouse studies can only take us so far,” says Kerstin.
“In our recent work at the Sanger, we have looked at the developing thymus, the organ in which particular immune cells, the T lymphocytes develop and learn how to distinguish between the body itself and invaders, such as pathogens or viruses. This exciting work may in the future allow us to control and fine-tune the activity of the immune system or to engineer new versions of T cells that are able to deal with specific diseases.”
The nature of science
We talked about what attracted Kerstin to join the Human Cell Atlas project at the Sanger Institute.
“The scale at which you can do things at Sanger is quite breath-taking,” she said. “Science requires a lot of attention to detail and therefore, if you work on your own, can be quite slow moving. But here I am part of a large, multidisciplinary and collaborative team, which I really enjoy. When you are part of a bigger- in this case global - team it is possible to make massive headway. We really are answering big questions.”
“In the Human Cell Atlas consortium, we encourage teams to collaborate, both with other groups in the Institute, and beyond, both nationally and internationally, and reach out to scientists across many different disciplines. This gets you to look at problems from different angles and I think it makes our science better.”
The theme of collaboration and openness is core to the Human Cell Atlas project. “The HCA is an Open Data project, there is a really big emphasis on that. It’s championed by the funders who support this work,” Kerstin explained.
“It’s something that’s really important to me. By making data available to others, you open the door to new ways of looking at it in the future, new analysis, or ways of twisting and shaping it, combining it with other data sets that could give insights. When you’ve spent a lot of money generating data, it should be used. There is no point it sitting in a computer. It needs to get out there.”
“People who’ve donated samples have a right to privacy which must be respected but whenever we can, and with the patient’s consent, we make the data as available as possible. It’s a public endeavour and I think it’s important that people who consent know that we will share our findings and results.”