Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo
Name
Pfau-2016-Aneuploidy impairs h.pdf
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Author(s)
Pfau, Sarah Jeanne
Silberman, Rebecca Estelle
Knouse, Kristin Ann
Amon, Angelika B.
Date Issued
June 2016
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Pfau, Sarah J. et al. “Aneuploidy Impairs Hematopoietic Stem Cell Fitness and Is Selected against in Regenerating Tissues in Vivo.” Genes & Development 30.12 (2016): 1395–1408.
Version
Final published version
Abstract
Aneuploidy, an imbalanced karyotype, is a widely observed feature of cancer cells that has long been hypothesized to promote tumorigenesis. Here we evaluate the fitness of cells with constitutional trisomy or chromosomal instability (CIN) in vivo using hematopoietic reconstitution experiments. We did not observe cancer but instead found that aneuploid hematopoietic stem cells (HSCs) exhibit decreased fitness. This reduced fitness is due at least in part to the decreased proliferative potential of aneuploid hematopoietic cells. Analyses of mice with CIN caused by a hypomorphic mutation in the gene Bub1b further support the finding that aneuploidy impairs cell proliferation in vivo. Whereas nonregenerating adult tissues are highly aneuploid in these mice, HSCs and other regenerative adult tissues are largely euploid. These findings indicate that, in vivo, mechanisms exist to select against aneuploid cells.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial 4.0 International
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DOI of Published Version
https://doi.org/10.1101/gad.278820.116
