Programming asynchronous replication in stem cells

Published on Dec 1, 2017in Nature Structural & Molecular Biology12.109
· DOI :10.1038/nsmb.3503
Hagit Masika4
Estimated H-index: 4
Marganit Farago7
Estimated H-index: 7
+ 6 AuthorsHoward Cedar73
Estimated H-index: 73
Asynchronous replication-timing patterns undergo programmed switching between maternal and paternal alleles in embryonic and adult stem cells.
  • References (53)
  • Citations (4)
📖 Papers frequently viewed together
15 Citations
5 Authors (Ying Chen, ..., Wenfeng Qian)
1 Citations
24 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Nathan Donley (OHSU: Oregon Health & Science University)H-Index: 8
#2Leslie S. Smith (OHSU: Oregon Health & Science University)H-Index: 25
Last. Mathew J. Thayer (OHSU: Oregon Health & Science University)H-Index: 22
view all 3 authors...
DNA replication initiates at multiple sites along each mammalian chromosome at different times during each S phase, following a temporal replication program. We have used a Cre/loxP-based strategy to identify cis-acting elements that control this replication-timing program on individual human chromosomes. In this report, we show that rearrangements at a complex locus at chromosome 15q24.3 result in delayed replication and structural instability of human chromosome 15. Characterization of this lo...
19 CitationsSource
#1Clara F. Alves-Pereira (IGC: Instituto Gulbenkian de Ciência)H-Index: 1
#2Raquel de Freitas (IGC: Instituto Gulbenkian de Ciência)H-Index: 1
Last. Vasco M. Barreto (IGC: Instituto Gulbenkian de Ciência)H-Index: 13
view all 7 authors...
How the vast majority of B cells express only one of the two alleles at their immunoglobulin loci remains a biological puzzle. Here, in mice reconstituted with a single haematopoietic stem cell, we demonstrate that each of the two immunoglobulin heavy chain (Igh) alleles has a similar probability to be the first to undergo VH to DJH rearrangement. We also observe this similar probability in clones from multipotent and common lymphoid precursors. The extreme biases in the expression of the allele...
9 CitationsSource
#1Thorsten BoroviakH-Index: 9
#2Ruth LoosH-Index: 111
Last. Jennifer NicholsH-Index: 51
view all 5 authors...
It has been unclear at which stage of mouse development embryonic stem cells can be derived. Nichols and colleagues use single-cell cultures to demonstrate that derivation of cells able to proliferate without ERK signalling (a characteristic of ESCs) is limited to the early pre-implantation epiblast and is favoured by culture on a laminin substrate.
228 CitationsSource
#1Deqiang Sun (BCM: Baylor College of Medicine)H-Index: 14
#2Min Luo (BCM: Baylor College of Medicine)H-Index: 11
Last. Margaret A. Goodell (BCM: Baylor College of Medicine)H-Index: 66
view all 17 authors...
Summary To investigate the cell-intrinsic aging mechanisms that erode the function of somatic stem cells during aging, we have conducted a comprehensive integrated genomic analysis of young and aged cells. We profiled the transcriptome, DNA methylome, and histone modifications of young and old murine hematopoietic stem cells (HSCs). Transcriptome analysis indicated reduced TGF-β signaling and perturbation of genes involved in HSC proliferation and differentiation. Aged HSCs exhibited broader H3K...
241 CitationsSource
#1Melanie A. Eckersley-Maslin (Watson School of Biological Sciences)H-Index: 5
#2David Thybert (EMBL-EBI: European Bioinformatics Institute)H-Index: 11
Last. David L. Spector (Watson School of Biological Sciences)H-Index: 77
view all 6 authors...
Random autosomal monoallelic gene expression refers to the transcription of a gene from one of two homologous alleles. We assessed the dynamics of monoallelic expression during development through an allele-specific RNA-sequencing screen in clonal populations of hybrid mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). We identified 67 and 376 inheritable autosomal random monoallelically expressed genes in ESCs and NPCs, respectively, a 5.6-fold increase upon differentiation. ...
69 CitationsSource
#1Anne-Valerie Gendrel (Curie Institute)H-Index: 8
#2Mikael Attia (Curie Institute)H-Index: 8
Last. Edith Heard (Curie Institute)H-Index: 61
view all 7 authors...
Summary X chromosome inactivation (XCI) and allelic exclusion of olfactory receptors or immunoglobulin loci represent classic examples of random monoallelic expression (RME). RME of some single copy genes has also been reported, but the in vivo relevance of this remains unclear. Here we identify several hundred RME genes in clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs during differentiation, and, once established, the monoallelic state can be highly stable. W...
72 CitationsSource
#1Ivan Rodriguez (University of Geneva)H-Index: 34
Understanding the mechanisms of monogenic and monoallelic transcription of the large repertoire of olfactory receptor genes represents a challenging task. A picture is now emerging in which odorant receptor choice and stabilization involve an escape from silencing followed by the activation of an unconventional feedback loop.
40 CitationsSource
#1Nathan Donley (OHSU: Oregon Health & Science University)H-Index: 8
#2Eric P. Stoffregen (OHSU: Oregon Health & Science University)H-Index: 17
Last. Mathew J. Thayer (OHSU: Oregon Health & Science University)H-Index: 22
view all 5 authors...
Mammalian chromosomes initiate DNA replication at multiple sites along their length during each S phase following a temporal replication program. The majority of genes on homologous chromosomes replicate synchronously. However, mono-allelically expressed genes such as imprinted genes, allelically excluded genes, and genes on female X chromosomes replicate asynchronously. We have identified a cis-acting locus on human chromosome 6 that controls this replication-timing program. This locus encodes ...
24 CitationsSource
#1Michal SlyperH-Index: 6
#2Amit ShaharH-Index: 2
Last. Ittai Ben-PorathH-Index: 18
view all 8 authors...
Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote their growth and progression. TCF3 (also known as TCF7L1) is a member of the TCF/LEF transcription factor family that is central in regulating epidermal and embryonic stem cell identity. We found that TCF3 is highly expressed in poorly differentiated human breast cancers, preferentially of the basal-like subtype. This suggested that TCF3 is involved in the regulati...
37 CitationsSource
#1Marganit FaragoH-Index: 7
#2Chaggai RosenbluhH-Index: 2
Last. Yehudit BergmanH-Index: 36
view all 16 authors...
Immunoglobulin genes are expressed from either the maternal or paternal chromosome; it is now shown that in early haematopoietic stem cells, an individual cell can choose either of the two alleles, but as they develop they become committed to only one.
34 CitationsSource
Cited By4
#1Claire Marchal (FSU: Florida State University)H-Index: 5
#2Jiao Sima (FSU: Florida State University)H-Index: 7
Last. David M. Gilbert (FSU: Florida State University)H-Index: 55
view all 3 authors...
The 3D organization of mammalian chromatin was described more than 30 years ago by visualizing sites of DNA synthesis at different times during the S phase of the cell cycle. These early cytogenetic studies revealed structurally stable chromosome domains organized into subnuclear compartments. Active-gene-rich domains in the nuclear interior replicate early, whereas more condensed chromatin domains that are largely at the nuclear and nucleolar periphery replicate later. During the past decade, t...
19 CitationsSource
#1Sharon Schlesinger (HUJI: Hebrew University of Jerusalem)H-Index: 6
#2Eran Meshorer (HUJI: Hebrew University of Jerusalem)H-Index: 33
Pluripotent embryonic stem cells (ESCs) are considered to have open and accessible chromatin relative to differentiated cells. However, as many studies supporting these conclusions relied on ESCs grown in serum, it has been suggested that some of these features are the result of culture conditions, particularly as more recent work using GSK3/MEK inhibitors ("2i") to mimic "ground-state" conditions of the pre-implantation blastocyst observed some altered epigenetic features. Here, we systematical...
6 CitationsSource
#1Nofar Mor (Weizmann Institute of Science)H-Index: 4
#2Yoach Rais (Weizmann Institute of Science)H-Index: 10
Last. Jacob H. Hanna (Weizmann Institute of Science)H-Index: 44
view all 30 authors...
Summary Mbd3, a member of nucleosome remodeling and deacetylase (NuRD) co-repressor complex, was previously identified as an inhibitor for deterministic induced pluripotent stem cell (iPSC) reprogramming, where up to 100% of donor cells successfully complete the process. NuRD can assume multiple mutually exclusive conformations, and it remains unclear whether this deterministic phenotype can be attributed to a specific Mbd3/NuRD subcomplex. Moreover, since complete ablation of Mbd3 blocks somati...
10 CitationsSource
#1Nofar Mor (Weizmann Institute of Science)H-Index: 4
#2Yoach Rais (Weizmann Institute of Science)H-Index: 10
Last. Jacob H. Hanna (Weizmann Institute of Science)H-Index: 44
view all 28 authors...
The Nucleosome Remodeling and Deacytelase (NuRD) complex is a co-repressive complex involved in many pathological and physiological processes in the cell. Previous studies have identified one of its components, Mbd3, as a potent inhibitor for reprogramming of somatic cells to pluripotency. Following OSKM induction, early and partial depletion of Mbd3 protein followed by applying naive ground-state pluripotency conditions, results in a highly efficient and near-deterministic generation of mouse i...
1 CitationsSource