Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells
TLDR
It is concluded that hES cell nuclei have a distinct nuclear architecture, especially at loci involved in maintaining pluripotency, which provides a framework within which other large-scale chromatin changes that may accompany differentiation can be considered.Abstract:
Nuclear organisation is thought to be important in regulating gene expression. Here we investigate whether human embryonic stem cells (hES) have a particular nuclear organisation, which could be important for maintaining their pluripotent state. We found that whereas the nuclei of hES cells have a general gene-density-related radial organisation of chromosomes, as is seen in differentiated cells, there are also distinctive localisations for chromosome regions and gene loci with a role in pluripotency. Chromosome 12p, a region of the human genome that contains clustered pluripotency genes including NANOG, has a more central nuclear localisation in ES cells than in differentiated cells. On chromosome 6p we find no overall change in nuclear chromosome position, but instead we detect a relocalisation of the OCT4 locus, to a position outside its chromosome territory. There is also a smaller proportion of centromeres located close to the nuclear periphery in hES cells compared to differentiated cells. We conclude that hES cell nuclei have a distinct nuclear architecture, especially at loci involved in maintaining pluripotency. Understanding this level of hES cell biology provides a framework within which other large-scale chromatin changes that may accompany differentiation can be considered.read more
Citations
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Journal ArticleDOI
Changes in chromosome territory position within the nucleus reflect alternations in gene expression related to embryonic lineage specification.
Maciej Orsztynowicz,Dorota Lechniak,Piotr Pawlak,Beata Kociucka,Svatava Kubickova,Halina Cernohorska,Zofia E. Madeja +6 more
TL;DR: Using bovine embryos as a model, the results suggest that large chromosomes regardless of their gene density do not significantly change their radial position within the nucleus, and that the observed changes in CT shape reflect global alternations in gene expression related to differentiation.
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Data-driven polymer model for mechanistic exploration of diploid genome organization
Yifeng Qi,Alejandro Reyes,Alejandro Reyes,Sarah E. Johnstone,Sarah E. Johnstone,Martin J. Aryee,Martin J. Aryee,Bradley E. Bernstein,Bradley E. Bernstein,Bin Zhang +9 more
TL;DR: The polymer model is introduced to study the organization of the diploid human genome, which is data-driven as all parameters can be derived from Hi-C data and a mechanistic model since the energy function is explicitly written out based on a few biologically motivated hypotheses.
Journal ArticleDOI
Arrangement of nuclear structures is not transmitted through mitosis but is identical in sister cells
Darya Y. Orlova,Lenka Stixová,Stanislav Kozubek,Hinco J. Gierman,Gabriela Šustáčková,Andrei V. Chernyshev,Ruslan N. Medvedev,Soňa Legartová,Rogier Versteeg,Pavel Matula,Pavel Matula,Roman Stoklasa,Eva Bártová +12 more
TL;DR: It is concluded that the arrangement of interphase chromatin is not transmitted through mitosis, but the nuclear pattern is identical in naturally synchronized sister cells.
Journal ArticleDOI
Microinjection of Antibodies Targeting the Lamin A/C Histone-Binding Site Blocks Mitotic Entry and Reveals Separate Chromatin Interactions with HP1, CenpB and PML.
TL;DR: The results indicate that lamin A-chromatin interactions are highly redundant and more diverse than generally acknowledged and highlight the importance of trying to experimentally separate their individual functions.
Journal ArticleDOI
Developmentally-poised chromatin of embryonic stem cells.
TL;DR: Current knowledge of Chromatin homeostasis in undifferentiated ES cells, and the remodeling of chromatin during the course of ES cell differentiation are outlined, and nuclear reprogramming activities in oocytes and ES cells are considered.
References
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James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
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Chunhui Xu,Margaret S. Inokuma,Jerrod Denham,Kathaleen Golds,Pratima Kundu,Joseph D. Gold,Melissa K. Carpenter +6 more
TL;DR: A successful feeder-free hES culture system in which undifferentiated cells can be maintained for at least 130 population doublings and are suitable for scaleup production is demonstrated.
Journal ArticleDOI
"Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells
TL;DR: The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells and provide a foundation for a more detailed understanding of stem cell biology.
Journal ArticleDOI
Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells
Jonathan S. Draper,Kath Smith,Paul J. Gokhale,Harry Moore,Edna Maltby,Julie A. Johnson,Lorraine F. Meisner,Thomas P. Zwaka,James A. Thomson,Peter W. Andrews +9 more
TL;DR: It is suggested that increased dosage of chromosome 17q and 12 gene(s) provides a selective advantage for the propagation of undifferentiated hES cells in transplantation therapies in which the use of aneuploid cells could be detrimental.
Journal ArticleDOI
Differences in the localization and morphology of chromosomes in the human nucleus
TL;DR: It is demonstrated that the distribution of genomic sequences between chromosomes has implications for nuclear structure and the findings are discussed in relation to a model of the human nucleus that is functionally compartmentalized.
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