37trillion is a number so large that it is simply impossible to grasp its enormity. Yet it is this number of cells, the smallest units of biological life, that form the coherent and conscious mass with which we are all closely familiar: the human body.

 

Now in a mission as equally as ambitious as the Human Genome Project, scientists are seeking to identify each of these cells and map its location within the body. It is hoped that the Human Cell Atlas might transform our understanding of our bodies just as the atlas transformed our understanding of the world.

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This is because our understanding of cells, like the first atlases, is incomplete. Our bodies depend upon on a huge variety of different cells to achieve everything we do, from moving to sleeping, thinking to eating. We know that cells belong to specialised types, each with varying forms and functions, and group together into tissues and organs which have broader and well understood roles in human physiology. However, much of the information about each cell type, such as where and in which tissues it is found, remain a mystery. This is where the Human Cell Atlas comes in:

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A complete Human Cell Atlas would give us a unique ID card for each cell type, a three-dimensional map of how cell types work together to form tissues, knowledge of how all body systems are connected, and insights into how changes in the map underlie health and disease. It would allow us to identify which genes associated with disease are active in our bodies and where, and analyze the regulatory mechanisms that govern the production of different cell types."

HumanCellAtlas.org

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Although the project has gained recent traction, the idea for the Atlas was conceived back in 2009 when Sarah Teichmann, head of cellular genetics at the Wellcome Sanger Institute, realised the importance of an emerging technique called single cell genomics. Using this technique, the gene expression profile or transcriptome of a single cell can be measured, providing a powerful new method to study and categorise cells.

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Previously, knowledge of cells has been acquired either by inspecting them under microscope, or more recently by analysing clumps of cells and finding their average properties. However, to truly understand the dynamic roles that different cells play, it is necessary to separate them and look at the molecules each cell produces, such as the RNA messenger molecules used to convert genes into proteins. Such a task would not have been possible a few years ago, but recent advances in the field now mean that single cells can be easily separated from different tissues and processed with extraordinary efficiency, with as many as 250 000 at once. 

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Although the field of single cell genomics remains is its infancy, its already beginning to transform cell biology, revealing significant differences between cells that were once thought to be genetically similar, if not identical. "There are so many cell types and cell states that we didn't know about, popping up unexpectedly when we use this technology," Teichmann told Wired, "It became clear that we could one day think about sampling all the cells in an organism as complex as the human." 

 

While Teichmann was busy in Cambridge, England, across the pond Aviv Regev, working at the Broad Institute in Cambridge, Massachusetts, had her sights set on the same goal.  Regev, a computational biologist, had begun to think about a collective project to systematically analyse all the cells in the body, circulating the idea in talks and seminars starting in 2014. The collaboration with Teichmann was formed two years following when the pair spoke, deciding to hold and meeting to gauge interest among the scientific community. Their proposal was enthusiastically received by a range of specialists – from software engineers to surgeons – all eager to become involved. The consortium now amasses over 1200 scientists and students and is a truly international effort.

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It wasn't long before the project was making groundbreaking discoveries. Working with Sam Behjati, also at the Sanger Institute, Teichmann used the profiling technique to examine kidney cells, revealing that cells found in Wilms' tumour, the most common childhood kidney cancer, closely resemble un-matured kidney cells. Their published research could result in a paradigm shift in how we treat this type of cancer, moving away from chemotherapies designed to kill cells to treatments intended to restore normal cell development and maturation. 

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In another surprising discovery, Regev and her collaborators at Massachusetts General Hospital identified a previously unknown type of cell in the lungs which they believe may be contributing to cystic fibrosis. Their findings, published in a pair of studies in Nature, reveal that these new cells could be main producers of CFTR – the protein whose absence or malformation leads to the symptoms of the disease. Again, this opens up major new avenues for helping to treat people with chronic conditions, giving a glimpse as to the further and future reaches of the project.

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“From the beginning we have designed this as a public good and an open resource to enable science around the world,” explains Regev. Like human genome for DNA, it was designed to be a useful reference for how healthy cells and tissues behave, however Regev believes the real potential lies in combining the atlas with data from diseased populations. “That’s where the interesting translational discoveries will be, much of which we cannot yet even imagine.” 

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