Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo
| Autor: | Angelika Amon, Rebecca E. Silberman, Sarah J. Pfau, Kristin A. Knouse |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Pfau, Sarah Jeanne, Silberman, Rebecca Estelle, Knouse, Kristin Ann, Amon, Angelika B. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aging Aneuploidy Cell Cycle Proteins Biology Protein Serine-Threonine Kinases medicine.disease_cause 03 medical and health sciences Mice Chromosome instability Chromosomal Instability Genetics medicine Leukocytes Animals Regeneration Cells Cultured Cell Proliferation Hematopoietic stem cell medicine.disease Hematopoietic Stem Cells Survival Analysis Cell biology Mice Inbred C57BL Haematopoiesis 030104 developmental biology medicine.anatomical_structure Cancer cell Mutation Stem cell Trisomy Carcinogenesis Developmental Biology Research Paper |
| Zdroj: | Cold Spring Harbor Laboratory Press |
| Popis: | 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. National Institutes of Health (U.S.) (CA206157) Kathy and Curt Marble Cancer Research Fund David H. Koch Institute for Integrative Cancer Research at MIT (Support Grant P30-CA14051) National Institute of General Medical Sciences (U.S.) (Training Grant T32GM007753) |
| Databáze: | OpenAIRE |
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