Abstract:
:Elucidating the molecular changes that arise during neural differentiation and fate specification is crucial for building accurate in vitro models of neurodegenerative diseases using human embryonic stem cells (hESCs). Here we review the importance of hESCs and derived progenitors in treating and modeling neurological diseases, and summarize the current efforts for the differentiation of hESCs into neural progenitors and defined neurons. We recapitulate the recent findings and discuss open questions on aspects of molecular control of gene expression by chromatin modification and methylation, posttranscriptional regulation by alternative splicing and the action of microRNAs, and protein modification. An integrative view of the different levels will hopefully provide much needed insight into understanding stem cell biology.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Yeo GW,Coufal N,Aigner S,Winner B,Scolnick JA,Marchetto MC,Muotri AR,Carson C,Gage FHdoi
10.1093/hmg/ddn065subject
Has Abstractpub_date
2008-04-15 00:00:00pages
R67-75issue
R1eissn
0964-6906issn
1460-2083pii
ddn065journal_volume
17pub_type
杂志文章,评审abstract::Three distinct regions, designated AZFa, b and c from proximal to distal Yq, are required for normal spermato-genesis in humans. Deletions involving AZFa (deletion interval 5C/D) seem to occur less frequently in infertile men and to be associated with a more severe testicular phenotype, with almost complete absence of...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.8.1161
更新日期:2000-05-01 00:00:00
abstract::We studied a large Danish family of seven generations in which autosomal dominant retinitis pigmentosa (adRP), a heterogeneous genetic form of retinal dystrophy, was segregating. After linkage had been excluded to all known adRP loci on chromosomes 3q, 6p, 7p, 7q, 8q, 17p, 17q and 19q, a genome screening was performed...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.8.1193
更新日期:1996-08-01 00:00:00
abstract::X-linked dilated cardiomyopathy (XLDCM) is a clinical phenotype of dystrophinopathy which is characterized by preferential myocardial involvement without any overt clinical signs of skeletal myopathy. To date, several mutations in the Duchenne muscular dystrophy gene, DMD , have been identified in patients with XLDCM,...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.7.1129
更新日期:1998-07-01 00:00:00
abstract::Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotroph...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh137
更新日期:2004-06-15 00:00:00
abstract::Glial cell line-derived neurotrophic factor (GDNF), a distant member of the TGF-beta superfamily, is a survival factor for various neurons, making it a potential therapeutic agent for neurodegenerative disorders. Here we present the genomic structure and characterization of the promoter of the human GDNF (hGDNF) gene....
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.12.1873
更新日期:1998-11-01 00:00:00
abstract::Limb-girdle muscular dystrophy type 2H (LGMD2H) and sarcotubular myopathy are hereditary skeletal muscle disorders caused by mutations in TRIM32. We previously identified TRIM32 as an E3 ubiquitin ligase that binds to myosin and ubiquitinates actin. To date four TRIM32 mutations have been linked to LGMD2H, all of whic...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp036
更新日期:2009-04-01 00:00:00
abstract::Small, submicroscopic, genomic deletions and duplications (1 kb to 10 Mb) constitute up to 15% of all mutations underlying human monogenic diseases. Novel genomic technologies such as microarray-based comparative genomic hybridization (array CGH) allow the mapping of genomic copy number alterations at this submicrosco...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddi268
更新日期:2005-10-15 00:00:00
abstract::Mutations in the gene encoding the inner nuclear membrane proteins lamins A and C produce cardiac and skeletal muscle dysfunction referred to as Emery Dreifuss muscular dystrophy. Lamins A and C participate in the LINC complex that, along with the nesprin and SUN proteins, LInk the Nucleoskeleton with the Cytoskeleton...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn386
更新日期:2009-02-15 00:00:00
abstract::Otosclerosis is a relatively common heterogenous condition, characterized by abnormal bone remodelling in the otic capsule leading to fixation of the stapedial footplate and an associated conductive hearing loss. Although familial linkage and candidate gene association studies have been performed in recent years, litt...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw106
更新日期:2016-06-15 00:00:00
abstract::Prolonged depolarization of skeletal muscle cells induces entry of extracellular calcium into muscle cells, an event referred to as excitation-coupled calcium entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine r...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq506
更新日期:2011-02-01 00:00:00
abstract::The Vesicle-associated membrane protein (VAMP)-Associated Protein B (VAPB) is the causative gene of amyotrophic lateral sclerosis 8 (ALS8) in humans. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective death of motor neurons leading to spasticity, muscle atrophy an...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt118
更新日期:2013-07-01 00:00:00
abstract::Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in ∼40% of patients. We hypothesized that unexplained IS cases represent a large collection of rare single-gene disorders. We investigated 44 children with unexplained IS using comparative genomic hybridisation arrays (aCGH) (n = 44) ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu199
更新日期:2014-09-15 00:00:00
abstract::Ciliary trafficking defects are the underlying cause of many ciliopathies, including Retinitis Pigmentosa (RP). Anterograde intraflagellar transport (IFT) is mediated by kinesin motor proteins; however, the function of the homodimeric Kif17 motor in cilia is poorly understood, whereas Kif7 is known to play an importan...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx143
更新日期:2017-07-01 00:00:00
abstract::The autosomal recessive mouse mutation retinal degeneration 6 (rd6) causes small, white retinal spots and progressive photoreceptor degeneration similar to that observed in human flecked retinal diseases. Using a positional cloning approach, we determined that rd6 mice carry a splice donor mutation in the mouse homolo...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.16.1879
更新日期:2002-08-01 00:00:00
abstract::Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a distinct variant within this group of autosomal recessive blistering skin diseases. In this study we demonstrate, for the first time, a homozygous mutation in the alpha6 integrin gene (ITGA6) in a family with three affected individuals. ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.5.669
更新日期:1997-05-01 00:00:00
abstract::We have studied 21 families with Wilson disease (WND), using restriction fragment length polymorphisms (RFLPs) in the 13q14.3 region, to measure linkage of these markers to the disease locus. In addition to previously described markers, we include linkage data for a newly isolated marker (D13S86) and an established ma...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.9.1401
更新日期:1993-09-01 00:00:00
abstract::Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh035
更新日期:2004-02-01 00:00:00
abstract::Paraspeckles are nuclear bodies formed by a set of specialized proteins assembled on the long non-coding RNA NEAT1; they have a role in nuclear retention of hyperedited transcripts and are associated with response to cellular stress. Fused in sarcoma (FUS) protein, linked to a number of neurodegenerative disorders, is...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt622
更新日期:2014-05-01 00:00:00
abstract::The fields of both developmental and stem cell biology explore how functionally distinct cell types arise from a self-renewing founder population. Multipotent, proliferative human neural crest cells (hNCC) develop toward the end of the first month of pregnancy. It is assumed that most differentiate after migrating thr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn235
更新日期:2008-11-01 00:00:00
abstract::We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.G...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu740
更新日期:2015-04-15 00:00:00
abstract::Ocular albinism type 1 (OA1) is an X-linked recessive disorder characterized by a major impairment of visual acuity, nystagmus, strabismus, photophobia and retinal hypopigmentation. From the analysis of patients carrying deletions and translocations involving the distal short arm of the X chromosome (Xp22.3) we have i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.3.373
更新日期:1995-03-01 00:00:00
abstract::A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated ove...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddm136
更新日期:2007-10-15 00:00:00
abstract::Parkinson's disease (PD) is a severe neurological disorder, characterized by the progressive degeneration of the dopaminergic nigrostriatal pathway and the presence of Lewy bodies (LBs). The discovery of genes responsible for familial forms of the disease has provided insights into its pathogenesis. Mutations in the p...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg159
更新日期:2003-06-15 00:00:00
abstract::X chromosome inactivation (XCI) is an epigenetic mechanism that silences the majority of genes on one X chromosome in females. Previous studies have suggested that the spread of XCI might be facilitated in part by common repeats such as long interspersed nuclear elements (LINEs). However, owing to the unusual sequence...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt553
更新日期:2014-03-01 00:00:00
abstract::Oculodentodigital syndrome (ODD) is a congenital, autosomal dominant disorder which affects the development of the face, eyes, limbs and dentition. Spastic paraparesis is thought to be an occasional manifestation of the disorder. Type III syndactyly, which occurs as part of ODD, has also been reported to occur as an i...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.1.123
更新日期:1997-01-01 00:00:00
abstract::Emerging evidence implicates epigenetic mechanisms in the pathogenesis of rheumatoid arthritis (RA). In this study, we have investigated the role of histone deacetylase (HDAC) enzymes in RA synovial fibroblasts (RASFs), a key cellular mediator of cartilage and bone destruction and determined effects of HDAC1 inhibitio...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv258
更新日期:2015-10-01 00:00:00
abstract::Alternative splicing emerges as one of the most important mechanisms to generate transcript diversity. It is regulated by the formation of protein complexes on pre-mRNA. We demonstrate that protein phosphatase 1 (PP1) binds to the splicing factor transformer2-beta1 (tra2-beta1) via a phylogenetically conserved RVDF se...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm284
更新日期:2008-01-01 00:00:00
abstract::Reduced sarcolemmal integrity in dystrophin-deficient muscles of mdx mice and Duchenne muscular dystrophy (DMD) patients has been reported to result in altered calcium homeostasis. Previous studies have shown a correlative relationship between calcium-dependent protease (calpain) activity in dystrophic muscle and musc...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.21.2645
更新日期:2002-10-01 00:00:00
abstract::Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz056
更新日期:2019-07-01 00:00:00
abstract::While the presence of a lipoyl-containing protein (protein X) separate from lipoyl transacetylase in the pyruvate dehydrogenase complex (PDC) has been known for some time, until recently only the cDNA for the yeast enzyme has been cloned. We have cloned, sequenced and characterized the cDNA encoding the human protein ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.3.501
更新日期:1998-03-01 00:00:00