Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells

被引:127
作者
Wiblin, AE
Cui, W
Clark, AJ
Bickmore, WA
机构
[1] MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland
[2] Roslin Inst, Roslin BioCtr, Roslin EH25 9PS, Midlothian, Scotland
关键词
centromere; chromosome territory; embryonic stem cell; NANOG; nucleus; OCT4;
D O I
10.1242/jcs.02500
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:3861 / 3868
页数:8
相关论文
共 43 条
[1]   The spatial organization of centromeric heterochromatin during normal human lymphopoiesis: evidence for ontogenically determined spatial patterns [J].
Alcobia, I ;
Quina, AS ;
Neves, H ;
Clode, N ;
Parreira, L .
EXPERIMENTAL CELL RESEARCH, 2003, 290 (02) :358-369
[2]   Spatial distribution patterns of interphase centromeres during retinoic acid-induced differentiation of promyelocytic leukemia cells [J].
Beil, M ;
Dürschmied, D ;
Paschke, S ;
Schreiner, B ;
Nolte, U ;
Bruel, A ;
Irinopoulou, T .
CYTOMETRY, 2002, 47 (04) :217-225
[3]   The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells [J].
Boyle, S ;
Gilchrist, S ;
Bridger, JM ;
Mahy, NL ;
Ellis, JA ;
Bickmore, WA .
HUMAN MOLECULAR GENETICS, 2001, 10 (03) :211-219
[4]   Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts [J].
Bridger, JM ;
Boyle, S ;
Kill, IR ;
Bickmore, WA .
CURRENT BIOLOGY, 2000, 10 (03) :149-152
[5]   Properties of four human embryonic stem cell lines maintained in a feeder-free culture system [J].
Carpenter, MK ;
Rosler, ES ;
Fisk, GJ ;
Brandenberger, R ;
Ares, X ;
Miura, T ;
Lucero, M ;
Rao, MS .
DEVELOPMENTAL DYNAMICS, 2004, 229 (02) :243-258
[6]   Chromosomal G-dark bands determine the spatial organization of centromeric heterochromatin in the nucleus [J].
Carvalho, C ;
Pereira, HM ;
Ferreira, J ;
Pina, C ;
Mendonça, D ;
Rosa, AC ;
Carmo-Fonseca, M .
MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (11) :3563-3572
[7]   Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription [J].
Chambeyron, S ;
Bickmore, WA .
GENES & DEVELOPMENT, 2004, 18 (10) :1119-1130
[8]   Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma [J].
Clark, AT ;
Rodriguez, RT ;
Bodnar, MS ;
Abeyta, MJ ;
Cedars, MI ;
Turek, PJ ;
Firpo, MT ;
Pera, RAR .
STEM CELLS, 2004, 22 (02) :169-179
[9]   Inheritance of gene density-related higher order chromatin arrangements in normal and tumor cell nuclei [J].
Cremer, M ;
Küpper, K ;
Wagler, B ;
Wizelman, L ;
von Hase, J ;
Weiland, Y ;
Kreja, L ;
Diebold, J ;
Speicher, MR ;
Cremer, T .
JOURNAL OF CELL BIOLOGY, 2003, 162 (05) :809-820
[10]   Non-random radial higher-order chromatin arrangements in nuclei of diploid human cells [J].
Cremer, M ;
von Hase, J ;
Volm, T ;
Brero, A ;
Kreth, G ;
Walter, J ;
Fischer, C ;
Solovei, I ;
Cremer, C ;
Cremer, T .
CHROMOSOME RESEARCH, 2001, 9 (07) :541-567