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The results, published in Nature, present a new opportunity to study, in humans, how stem cells throughout the body change during aging and disease. By using whole-genome sequencing to construct and analyze a family tree of cells, this work could lead to a better understanding of how cancers develop and why some stem cell-based therapies are more effective than others.
All the organs in our body depend on stem cells to maintain their function. Adult stem cells in tissues or organs are an autonomous population of cells whose offspring produce all types of specialized cells in a tissue.
Blood stem cells stimulate blood production and are used in treatments and treatments such as bone marrow transplants – a treatment against leukemia that replaces cancerous blood cells with healthy blood stem cells.
However, human blood stem cells are not fully understood, although some of the most basic issues, such as the number of cells present and their evolution with age, have not been fully understood. not yet resolved.
For the first time, scientists have been able to determine how many blood stem cells actively contribute to the health of a human being. The researchers adapted a method traditionally used in ecology to track the size of the population to estimate that a healthy adult has between 50,000 and 200,000 stem cells contributing to their blood cells at a time.
"We found that healthy adults have between 50,000 and 200,000 blood stem cells, about ten times as much as we thought before. While previous estimates of the number of blood stem cells have been extrapolated from studies in mice, cats or monkeys, this is the first time that the number of stem cells has been directly quantified in the man. This new approach paves the way for the study of stem cells in other human organs and their evolution between health and disease and as we age.
Dr. Peter Campbell, Lead Author and Co-Leader of the Wellcome Sanger Institute Cancer Genome Project Team
Scientists have found that the number of stem cells in the blood increases rapidly during childhood and reaches a plateau in adolescence. The number of stem cells remains relatively constant in adulthood.
In the study, the researchers performed 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 blood cell population.
"We isolated several stem cells from the blood and bone marrow and sequenced their genomes to find mutations. Mutations act as barcodes, each uniquely identifying a stem cell and its descendants. We then looked for these mutations in the rest of the blood to see which fraction of the blood cells had the same bar codes, and from there we could estimate the total number of stem cells.
Henry Lee-Six, the first author of the Wellcome Sanger Institute
Current methods for measuring the size of stem cell populations usually involve genome engineering, which means that they are limited to model organisms, such as mice. By analyzing natural mutations in human cells, researchers can use the accumulation of mutations to track stem cells to see how stem cell dynamics change over a person's life.
"This new approach is extremely flexible. Not only can we measure the number of existing stem cells, but we can also see how they are related to each other and what types of blood cells they produce. By applying this technique to samples from patients with blood cancers, we should now be able to learn how individual cells outperform normal cells to increase their numbers and lead to cancer. As the cost of genomic sequencing decreases, it is transforming scientific research so that the studies hitherto thought to be extremely important are now becoming routine. It's a very exciting time to work in this space.
Dr. David Kent, co-lead author of the Wellcome-MRC Cambridge Stem Cell Institute and the Department of Hematology at the University of Cambridge
Picture: A colony of blood cells derived from a single isolated cell in a 59-year-old man. Image credit: Mairi Shepherd, Kent Lab
* Capture-recapture is a method commonly used in ecology to estimate the population size of a species. Part of the population is captured, labeled and released. Later, another part is captured and the number of individuals marked in the sample is counted. Since the number of individuals marked in the second sample should be proportional to the number of individuals marked in the overall population, one can obtain an estimate of the total population size by dividing the number of individuals marked by the proportion of individuals marked in the second. sample. https://en.wikipedia.org/wiki/Mark_and_recapture
Publication:
Henry Lee-Six et al. (2018) Dynamics of the normal human blood population derived from somatic mutations. Nature. DOI: 10.1038 / s41586-018-0497-0
Funding:
This work was supported by the Leukemia Lymphoma Society, Wellcome, Bloodwise and other donors. Please see the paper for the complete list of funders.
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