Abstract:
:The discovery of induced pluripotent stem cells (iPSCs) has solidified the concept of transcription factors as major players in controlling cell identity and provided a tractable tool to study how somatic cell identity can be dismantled and pluripotency established. A number of landmark studies have established hallmarks and roadmaps of iPSC formation by describing relative kinetics of transcriptional, protein and epigenetic changes, including alterations in DNA methylation and histone modifications. Recently, technological advancements such as single-cell analyses, high-resolution genome-wide chromatin assays and more efficient reprogramming systems have been used to challenge and refine our understanding of the reprogramming process. Here, we will outline novel insights into the molecular mechanisms underlying iPSC formation, focusing on how the core reprogramming factors OCT4, KLF4, SOX2 and MYC (OKSM) drive changes in gene expression, chromatin state and 3D genome topology. In addition, we will discuss unexpected consequences of reprogramming factor expression in in vitro and in vivo systems that may point towards new applications of iPSC technology.
journal_name
Curr Opin Genet Devjournal_title
Current opinion in genetics & developmentauthors
Apostolou E,Stadtfeld Mdoi
10.1016/j.gde.2018.06.002subject
Has Abstractpub_date
2018-10-01 00:00:00pages
77-85eissn
0959-437Xissn
1879-0380pii
S0959-437X(17)30126-0journal_volume
52pub_type
杂志文章,评审abstract::Bioinformatics is now an essential tool in many aspects of human molecular genetics research. Methods for the prediction of gene structure are essential components in genomic sequencing projects and provide the key to deriving protein sequence and locating intron/exon junctions. Sequence comparison and database search...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/s0959-437x(97)80158-x
更新日期:1997-06-01 00:00:00
abstract::Family-based next generation sequencing (NGS) has recently pointed to an important role for de novo germline point mutations in both rare and common genetic disorders associated with reduced fitness. In this review we highlight the impact of the mutational target size on the frequency of diseases caused by these de no...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2013.01.007
更新日期:2013-06-01 00:00:00
abstract::Life-long neurogenesis is highly restricted to specialized niches in the adult mammalian brain and therefore the brain's capacity for spontaneous regeneration is extremely limited. However, recent work has demonstrated that under certain circumstances parenchymal astrocytes and NG2 glia can generate neuronal progeny. ...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2015.07.004
更新日期:2015-10-01 00:00:00
abstract::The genomic perspective aids in integrating the analysis of single resistance (R-) genes into a higher order model of complex plant resistance systems. The majority of R-genes encode a class of proteins with nucleotide binding (NB) and leucine-rich repeat (LRR) domains. Several R-proteins act in multi-protein R-comple...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2007.08.014
更新日期:2007-12-01 00:00:00
abstract::Logical models provide insight about key control elements of biological networks. Based solely on the logical structure, we can determine state transition diagrams that give the allowed possible transitions in a coarse grained phase space. Attracting pathways and stable nodes in the state transition diagram correspond...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2010.09.005
更新日期:2010-12-01 00:00:00
abstract::Since the recognition of the uniqueness and coherence of the archaebacteria (sometimes called Archaea), our perception of their role in early evolution has been modified repeatedly. The deluge of sequence data and rapidly improving molecular systematic methods have combined with a better understanding of archaebacteri...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/0959-437x(94)90065-5
更新日期:1994-12-01 00:00:00
abstract::After fertilization, mouse embryos go through preimplantation development to give rise to blastocyst. Two key molecular events, zygotic genome activation (ZGA) and the first cell lineage specification, are essential for the process. Recent advances in low-input epigenomics profiling techniques allow the analysis of th...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2020.05.015
更新日期:2020-10-01 00:00:00
abstract::Segmentation in Drosophila is a sequential process directed by at least 30 genes that encode various types of proteins, including: many transcription factors; a putative RNA-binding protein; a membrane-associated receptor kinase; several intracellular protein kinases; a number of secreted signaling molecules; and othe...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/0959-437x(93)90094-6
更新日期:1993-08-01 00:00:00
abstract::In their development, plants precisely control the patterns of cell size, cell shape and cell division, the position of differentiation of cell types, and the position and number of organs. In the past year, progress has been made in understanding four of these five levels of control of plant pattern formation, includ...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/0959-437x(94)90079-i
更新日期:1994-08-01 00:00:00
abstract::Our understanding of how roots develop in soil may be at the eve of significant transformations. The formidable expansion of imaging technologies enables live observations of the rhizosphere micro-pore architecture at unprecedented resolution. Granular matter physics provides ways to understand the microscopic fluctua...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2018.03.007
更新日期:2018-08-01 00:00:00
abstract::The pattern of expression of homeodomain proteins often exceeds their apparent domain of activity. Tissue-specific proteins that modulate the in vivo activity of homeodomain proteins have been proposed to account for this functional restriction. The first identified example of such an accessory protein is DCoH, which ...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/0959-437x(93)90030-s
更新日期:1993-04-01 00:00:00
abstract::TGFβ acts as a potent tumor suppressor and tumor promoter in a context dependent manner. Tumor suppressive functions include inhibition of cell proliferation, induction of apoptosis and regulation of autophagy. As tumors develop they switch their response to TGFβ and utilise this factor as a potent promoter of cell mo...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2010.12.004
更新日期:2011-02-01 00:00:00
abstract::The advent of methods for mapping the location of specific proteins across genomes is substantially enlightening our understanding of gene regulation. One recent discovery is that Pol II is concentrated at the 5' end of thousands of genes in mammalian and Drosophila cells. Before this, much research had focused on und...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2011.01.010
更新日期:2011-04-01 00:00:00
abstract::The sequences of both of the human sex chromosomes and of a substantial part of the chimpanzee Y chromosome have now been determined, and most of the protein-coding genes have been identified. The X chromosome codes for more than 800 proteins but the Y chromosome for only approximately 60, illustrating their very diff...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2006.04.006
更新日期:2006-06-01 00:00:00
abstract::Control of protein synthesis (mRNA translation) is essential for proper brain development and function. Perturbations to the mechanisms governing mRNA translation have repeatedly been shown to constitute a neurodegenerative, neuropsychiatric, and neurodevelopmental disorder risk factor. Developing effective therapeuti...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2020.05.005
更新日期:2020-12-01 00:00:00
abstract::Cellular phenotypes can critically rely on mono-allelic gene expression. Recent studies suggest that in mammalian cells inter-chromosomal DNA interactions may mediate the decision which allele to activate and which to silence. Here, these findings are discussed in the context of knowledge on gene competition, chromati...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2007.07.009
更新日期:2007-10-01 00:00:00
abstract::During development and differentiation, early inductive processes that influence cell fate at a later stage leave marks at distinct gene loci that are maintained through several rounds of mitosis. The structure of chromatin is part of this epigenetic memory that restricts or permits differential expression of genes in...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/s0959-437x(00)00175-1
更新日期:2001-04-01 00:00:00
abstract::The establishment of left-right asymmetries in the vertebrate embryo is carried out by complex genetic interactions that impart left- or right-sided information to the developing organs and structures. The origin of LR information is still unclear, but recent advances have provided new insights as to how it is relayed...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2004.07.011
更新日期:2004-10-01 00:00:00
abstract::Investigations on chromatin assembly in vitro implicate chromatin assembly factor 1 (CAF1) as a chaperone for histones H3/H4 and nucleosome assembly protein 1 (NAP1) as a chaperone for histones H2A/H2B. Deletion analysis of CAF1 in vivo suggests multiple redundant pathways for deposition of the histones. Histone depos...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/S0959-437X(99)80028-8
更新日期:1999-04-01 00:00:00
abstract::Chromatin-based epigenetic inheritance cooperates with cis-acting DNA sequence information to propagate gene expression states and chromosome architecture across cell division cycles. Histone proteins and their modifications are central components of epigenetic systems but how, and to what extent, they are propagated ...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2012.11.002
更新日期:2013-04-01 00:00:00
abstract::Significant advances in the field of hepatocyte-specific gene expression have been made during the past year. Several new transcription factors have been cloned and partially characterized. Analyses of the promoter regions of several factors have also been initiated and Drosophila homologs for two of these factors hav...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/s0959-437x(05)80282-5
更新日期:1992-04-01 00:00:00
abstract::In the Drosophila eye, photoreceptor clusters are arranged with mirror-image symmetry about the dorso-ventral midline. Recent work indicates critical rôles for Wingless and JAK/STAT signalling in setting up long-range gradients of positional information that determine this symmetry. Furthermore, important functions ha...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/S0959-437X(99)80067-7
更新日期:1999-08-01 00:00:00
abstract::Recent advances in cell reprogramming via employing different sets of factors, which allows generation of various cell types that are beyond the downstream developmental lineages from the starting cell type, provide significant opportunities to study fundamental biology and hold enormous promise in regenerative medici...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2014.09.006
更新日期:2014-10-01 00:00:00
abstract::Studies of primate lentivirus phylogeny over the past decade have established a minimum of five related, but genetically distinct, groups of simian immunodeficiency virus (SIV), each originating from a different African primate species. The hypothesis that HIV-2 (and SIVmac) arose by cross-species transmission from so...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/0959-437x(95)80014-v
更新日期:1995-12-01 00:00:00
abstract::Cancer remains one of the leading causes of death in the developed world and despite impressive advances in therapeutic modalities, only a small subset of patients are currently cured. The underlying genetic heterogeneity of cancers clearly plays a crucial role in determining both the clinical course of individual pat...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2020.02.012
更新日期:2020-02-01 00:00:00
abstract::The discovery that rare POT1 variants are associated with extremely long telomeres and increased cancer predisposition has provided a framework to revisit the relationship between telomere length and cancer development. Telomere shortening is linked with increased risk for cancer. However, over the past decade, there ...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/j.gde.2020.02.002
更新日期:2020-02-01 00:00:00
abstract::Microarray technologies enable genome-scale expression measurements. Already proved to be of value for the functional analysis of individual genes and biological processes, the application of expression profiling to disease gene discovery is now growing in importance and practicality. ...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/s0959-437x(00)00187-8
更新日期:2001-06-01 00:00:00
abstract::The PML and SP100-containing nuclear bodies (NBs) represent the best-studied example of a defined nuclear substructure the integrity of which is compromised in certain human diseases, including leukemia, neurodegenerative disorders and viral infection. Although recent progress has underscored the unexpectedly broad in...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/s0959-437x(99)80054-9
更新日期:1999-06-01 00:00:00
abstract::Following neurulation, neural crest cells emerge from the neural tube and undergo extensive migrations. At the onset of migration, multipotent stem cells exist within the neural crest population. Eventually, these assume one of a number of possible fates, ranging from neurons and glia of the peripheral nervous system ...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/0959-437x(93)90101-t
更新日期:1993-08-01 00:00:00
abstract::DNA methylation and chromatin modification are two global mechanisms that regulate gene expression. Recent studies provide insight into the mechanism of transcriptional silencing by a methyl-CpG binding protein, MeCP2. MeCP2 is shown to interact with the Sin3/histone deacetylase co-repressor complex. Thus, this intera...
journal_title:Current opinion in genetics & development
pub_type: 杂志文章,评审
doi:10.1016/s0959-437x(99)80024-0
更新日期:1999-04-01 00:00:00