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Tracking hematopoietic stem cells and their progeny using whole-genome sequencing

Authors
  • Lee-Six, Henry1
  • Kent, David G.2, 3, 4
  • 1 Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
  • 2 York Biomedical Research Institute, Department of Biology, University of York, York, United Kingdom
  • 3 Wellcome MRC Cambridge Stem Cell Institute, University of Cambridge, Hills Road, Cambridge, United Kingdom
  • 4 Department of Haematology, University of Cambridge, Cambridge, United Kingdom
Type
Published Article
Journal
Experimental Hematology
Publisher
Elsevier Science Inc
Publication Date
Mar 01, 2020
Volume
83
Pages
12–24
Identifiers
DOI: 10.1016/j.exphem.2020.01.004
PMID: 32007478
PMCID: PMC7118367
Source
PubMed Central
License
Unknown

Abstract

Despite decades of progress in our understanding of hematopoiesis through the study of animal models and transplantation in humans, investigating physiological human hematopoiesis directly has remained challenging. Questions on the clonal structure of the human hematopoietic stem cell (HSC) pool, such as “how many HSCs are there?” and “do all HSC clones actively produce all blood cell types in equal proportions?” remain open. These questions have inherent value for understanding normal human physiology, but also directly inform our comprehension of the process by which the system is subverted to drive diseases of the blood, in particular blood cancers and bone marrow failure syndromes. The critical link between normal and abnormal hematopoiesis is perhaps best illustrated by the recent discovery of clonal hematopoiesis in healthy people with no abnormal blood parameters. In such individuals, large clones derived from single cells are present and are dominant relative to their normal counterparts, but their presence does not necessitate abnormal blood cell production. Intriguingly, however, these individuals are also at a significantly greater risk of developing leukemias and of cardiovascular events, underscoring the importance of understanding how blood stem cell clones compete against each other.

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