title: Nuclear organisation in totipotent human nuclei and its relationship to chromosomal abnormality.
abstract: Studies of nuclear organisation, most commonly determining the nuclear location of chromosome territories and individual loci, have furthered our understanding of nuclear function, differentiation and disease. In this study, by examining eight loci on different chromosomes, we tested hypotheses that: (1) totipotent human blastomeres adopt a nuclear organisation akin to that of committed cells; (2) nuclear organisation is different in chromosomally abnormal blastomeres; and (3) human blastomeres adopt a ;chromocentre' pattern. Analysis of in vitro fertilisation (IVF) conceptuses permits valuable insight into the cell biology of totipotent human nuclei. Here, extrapolations from images of preimplantation genetic screening (PGS) cases were used to make comparisons between totipotent blastomeres and several committed cells, showing some differences and similarities. Comparisons between chromosomally abnormal nuclei and those with no detected abnormality (NDA) suggest that the former display a significant non-random pattern for all autosomal loci, but there is a less distinct, possibly random, pattern in 'NDA' nuclei. No evidence was found that the presence of an extra chromosome is accompanied by an altered nuclear location for that chromosome. Centromeric loci on chromosomes 15 and 16 normally seen at the nuclear periphery were mostly centrally located in aneuploid cells, providing some evidence of a 'chromocentre'; however, the chromosome-18 centromere was more peripheral, similar to committed cells. Our results provide clues to the nature of totipotency in human cells and might have future applications for preimplantation diagnosis and nuclear transfer.
authors.affiliation: Department of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK.
authors.forename: Katie A
authors.initials: KA
authors.lastname: Finch
authors.forename: Gothami
authors.initials: G
authors.lastname: Fonseka
authors.forename: Dimitris
authors.initials: D
authors.lastname: Ioannou
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hickson
authors.forename: Zoe
authors.initials: Z
authors.lastname: Barclay
authors.forename: Katerina
authors.initials: K
authors.lastname: Chatzimeletiou
authors.forename: Anna
authors.initials: A
authors.lastname: Mantzouratou
authors.forename: Alan
authors.initials: A
authors.lastname: Handyside
authors.forename: Joy
authors.initials: J
authors.lastname: Delhanty
authors.forename: Darren K
authors.initials: DK
authors.lastname: Griffin
mesh_terms: D000782:Aneuploidy; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D001757:Blastomeres / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D002478:Cells, Cultured; D002503:Centromere / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002869:Chromosome Aberrations / Q000196:embryology*; D002874:Chromosome Mapping / Q000379:methods; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D020732:Cytogenetic Analysis; D047108:Embryonic Development / Q000235:genetics; D006801:Humans; D008297:Male; D039901:Totipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D014407:Tumor Cells, Cultured