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Aneuploidy in Embryonic Stem Cells

  • Rafaela C. Sartore
  • Priscila B. Campos
  • Michael J. McConnell
  • Stevens K. RehenEmail author
Chapter

Abstract

Aneuploidy is defined as the loss and/or gain of chromosomes to produce a numerical deviation from multiples of the haploid chromosomal complement. This phenomenon can be classified as a net increase in chromosome number, referred to as hyperploidy, or a net decrease, referred to as hypoploidy. Biologically, chromosome number can range from 0 (red blood cells) to polyploidy (hepatocytes, neoplasms). Human embryonic stem cells (hES) have great potential for use in both basic science and therapeutic strategies, including transplantation for regenerative medicine. A challenge for cell therapy using hES is the maintenance of stable cell lines, particularly following extended passaging. Chromosomal instability has recently been reported in hES, resulting from clonal expansion of aneuploid cells. It includes hyperploidies, particularly trisomies of chromosomes 12, 17 or 20 and, to a lesser extent, chromosome loss. The generality of this phenomenon is uncertain and it is currently unclear whether aneuploidy in stem cell lines is in fact deleterious. What is the physiological significance or therapeutic risk associated with hES aneuploidy? Here, features of cell cycle and the relevance of aneuploidy are discussed on regard of its implications for the physiology and therapeutic purposes of embryonic stem cells.

Keywords

Aneuploidy Cancer stem cells Cell cycle checkpoint Embryonic stem cells Genome integrity 

Abbreviations

AD

Alzheimer’s disease

APC/C

anaphase promoting complex-cyclosome

ATM

ataxia telangiectasia-mutated protein kinase

Bub

Budding Uninhibited by Benzimidazole

CSC

cancer stem cell(s)

Cdc

Cell division control protein

Chk

Checkpoint kinase

CDK

Cyclin-dependent kinase activity

CKI

Cyclin Kinase Inhibitors

dNTP

deoxyribonucleotide triphosphate(s)

EB

Embryoid Bodies

EC cell(s)

Embryonal Carcinoma cell(s)

ES cell(s)

Embryonic Stem cell(s)

FISH

Fluorescence In Situ Hybridization

G phases

Gap phases

pRb

Retinoblastoma protein

IVF

In Vitro Fertilization

mEF

mouse embryonic fibroblast(s)

CENP-E

Microtubule-dependent motor centromere-associated protein E

Mps1

Mitogen-activated protein kinase 1

M phase

Mitosis phase

Mad

Mitotic arrest deficient

MVA

Mosaic Variegated Aneuploidy

NPC

neural progenitor cell(s)

OCT-4

Octamer-binding transcription factor 4

p19/ARF

p19 alternative reading frame protein

SAC

Spindle Assembly Checkpoint

SSEA-1

Stage-Specific Embryonic Antigen 1

S phase

Synthesis phase

p53

(53 kilodalton) tumor suppressor protein

Notes

Acknowledgements

We thank Stacie Ngo Abdalla for manuscript editing. This work was supported by grants from Faperj – Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (S.R.), CNPq – Conselho Nacional para o Desenvolvimento Científico e Tecnológico (R.S., P.B., S.R.), Pew Latin American Program in Biomedical Sciences (S.R.) and Brazilian Ministry of Health/DECIT (S.R.).

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Rafaela C. Sartore
    • 1
  • Priscila B. Campos
    • 1
  • Michael J. McConnell
    • 2
  • Stevens K. Rehen
    • 1
    Email author
  1. 1.Instituto de Ciências BiomédicasUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.Crick-Jacobs Center for Theoretical and Computational BiologySalk Institute for Biological StudiesLa JollaUSA

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