Somatic Mutations as Markers for Size and Lifetimes of Blood Stem Cells

By Riya Gandhi ‘22

stem-cell.jpg

Figure 1. Examples of haematopoietic stem cells include white blood cells in bone marrow.

Despite the importance of hematopoiesis — a process that balances production and destruction of specialized blood cells — in the human body, scientists were unable to quantify the population size and lifetime dynamics that govern the process until now.

Researchers from the Wellcome-Trust Sanger Institute, Wellcome-MRC Cambridge Stem Cell Institute, and the University of Cambridge conducted a recent study under principle investigators Dr. Anthony Green, Dr. David Kent, and Dr. Peter Campbell. These researchers inferred that somatic cell mutations could be markers for quantifying number, activity, and lifetimes of blood stem cells because such mutations are inherited in descendant cells and thereby create an accurate molecular clock. In the first phase of the experiment, the researchers captured a hematopoietic stem cell and a progenitor cell from a bone marrow aspirate and peripheral blood draw from a 59-year old male. The researchers then allowed the cells to proliferate into colonies and performed whole-genome sequencing to identify somatic mutations. In the recapture phase, bulk populations of granulocytes and B and T lymphocytes were isolated at three time points and one time point, respectively. Deep targeted sequencing was then performed for the somatic mutations discovered in the first phase and a phylogenetic tree constructed. From the analysis of these results, the researchers confirmed that adult hematopoiesis is an arrangement of embryonic clones that are derived from the fertilized egg. They compared these findings to the lineage-marking studies done in mice and were able to estimate that the number of stem cells that contribute to human hematopoiesis is in the hundreds of thousands.

The researchers hope to collect more colonies in the future to uncover the differences between myeloid and T cell production. They project that their discovery may lead to the ability to engineer or extend lifetimes of these stem cells in the human body and thereby provide patients who suffer from haematopoietic diseases with a better chance at recovery.

 

References

  1. H. Lee-Six, et. al., Population dynamics of normal human blood inferred from somatic mutations. Nature (2018). doi: https://doi.org/10.1038/s41586-018-0497-0.  
  2. Image retrieved from: https://www.pexels.com/photo/white-and-clear-glass-syringe-161628/
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