12 September 2018

Adult humans have ten times the haematopoietic stem cells in their bone marrow than previously thought, British scientists have reported.

A new approach for studying stem cells based on methods used in ecology, developed by researchers at Wellcome Sanger Institute and Wellcome-MRC Cambridge Stem Cell Institute, has shown that a healthy adult has between 50,000 and 200,000 stem cells contributing to their blood cells at any one time. The findings, published in Nature, open up new opportunities for studying how stem cells change in humans during ageing and disease.

The study used whole genome sequencing to build and analyse a family tree of cells, and could lead to further research into how cancers develop and why some stem cell therapies are more effective than others.

The research team conducted whole genome sequencing on 140 blood stem cell colonies from a healthy 59-year-old man. The team adapted a ‘capture-recapture’ method, traditionally used in ecology to monitor species populations, to ‘tag’ stem cells and compare them to the population of blood cells.

First author Henry Lee-Six, from the Wellcome Sanger Institute, said they isolated a number of stem cells from the blood and bone marrow and sequenced their genomes to find mutations.

 “The mutations act like barcodes, each of which uniquely tags a stem cell and its descendants,” he said.

 “We then looked for these mutations in the rest of the blood to see what fraction of blood cells carry the same barcodes and from this, we could estimate how many stem cells there were in total.”

They found the number of stem cells in the blood increases rapidly through childhood and reaches a plateau by adolescence. The number of stem cells stays relatively constant throughout adulthood.

Dr Peter Campbell, a joint leader of the study from the Wellcome Sanger Institute, said: "We discovered that healthy adults have between 50,000 and 200,000 blood stem cells, which is about ten times more than previously thought.

 “Whereas previous estimates of blood stem cell numbers were extrapolated from studies in mice, cats or monkeys, this is the first time stem cell numbers have been directly quantified in humans. This new approach opens up avenues into studying stem cells in other human organs and how they change between health and disease, and as we age.”

Dr David Kent, a joint leader of the study from the Wellcome-MRC Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, said the new approach is flexible because it enables scientists to measure how many stem cells exist and to see how related they are to each other and what types of blood cells they produce.

 “Applying this technique to samples from patients with blood cancers, we should now be able to learn how single cells outcompete normal cells to expand their numbers and drive a cancer,” he said.

 “As the cost of genomic sequencing comes down, it is transforming scientific research such that studies previously thought to be impossibly large, are now becoming routine.”

Source: Lee-Six, H., Øbro, N.F., Shepherd, M.S., Grossmann, S., Dawson, K., Belmonte, M., Osborne, R.J., Huntly, B.J.P., Martincorena, I., Anderson, E., O'Neill, L., Stratton, M.R., Laurenti, E., Green, A.R., Kent, D.G., Campbell, P.J. (2018) ‘Population dynamics of normal human blood inferred from somatic mutations’, Nature. Available at doi: 10.1038/s41586-018-0497-0


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