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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Genome-wide reduction in H3K9 acetylation during human embryonic stem cell differentiation.
Jana Krejčí,Radka Uhlírová,Gabriela Galiová,Stanislav Kozubek,Jana Šmigová,Jana Šmigová,Eva Bártová +6 more
TL;DR: ChIP‐on‐chip analysis revealed that differentiation results in a genome‐wide decrease in promoter H3K9 acetylation, and analyses point to chromosomes 11, 12, 17, and 19 as being critical for hESC pluripotency and endoderm‐like differentiation.
Journal ArticleDOI
ICR Noncoding RNA Expression Controls Imprinting and DNA Replication at the Dlk1-Dio3 Domain
Satya K. Kota,David Llères,Tristan Bouschet,Ryutaro Hirasawa,Alice Marchand,Christina Begon-Pescia,Ildem Sanli,Philippe Arnaud,Laurent Journot,Michael Girardot,Robert Feil +10 more
TL;DR: It is found that in mouse embryonic stem cells (ESCs) and in blastocysts, this function is linked to maternal, bidirectional expression of noncoding RNAs (ncRNAs) from the ICR.
Journal ArticleDOI
The Impact of Centromeres on Spatial Genome Architecture.
TL;DR: The structures and functions of centromeres in various organisms are shared beginning with the diversity of their DNA sequence anatomies and ultimately detail the different ways they contribute to genome organization and regulation at the spatial level.
Journal ArticleDOI
Epigenome and chromatin structure in human embryonic stem cells undergoing differentiation
TL;DR: Pluripotent and differentiated hESCs have distinct nuclear patterns of heterochromatic structures and epigenetic marks, while relatively conserved gene density‐related radial chromatin distributions are already largely established in undifferentiated hES cells.
Journal ArticleDOI
Cell type specific chromosome territory organization in the interphase nucleus of normal and cancer cells.
TL;DR: The findings of highly preferred chromosome association profiles that are cell type specific and undergo alterations in cancer cells, lead us to propose a probabilistic chromosome code whereby the 3‐D association profile of chromosomes contributes to the functional landscape of the cell nucleus, the global regulation of gene expression and the epigenetic state of chromatin.
References
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Embryonic Stem Cell Lines Derived from Human Blastocysts
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.
Journal ArticleDOI
Feeder-free growth of undifferentiated human embryonic stem cells.
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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