Abstract:
:Cockayne syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features, including increased sensitivity to sunlight, progressive neurological abnormalities, and the appearance of premature aging. However, the pathogenesis of CS remains unclear due to the limitations of current disease models. Here, we generate integration-free induced pluripotent stem cells (iPSCs) from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic gene-corrected CS-iPSCs (GC-iPSCs) using the CRISPR/Cas9 system. CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells (MSCs) and neural stem cells (NSCs), both of which display increased susceptibility to DNA damage stress. Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6. We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives (MSCs and NSCs) in the absence or presence of ultraviolet (UV) and replicative stresses, revealing that defects in DNA repair account for CS pathologies. Moreover, we generate autologous GC-MSCs free of pathogenic mutation under a cGMP (Current Good Manufacturing Practice)-compliant condition, which hold potential for use as improved biomaterials for future stem cell replacement therapy for CS. Collectively, our models demonstrate novel disease features and molecular mechanisms and lay a foundation for the development of novel therapeutic strategies to treat CS.
journal_name
Protein Celljournal_title
Protein & cellauthors
Wang S,Min Z,Ji Q,Geng L,Su Y,Liu Z,Hu H,Wang L,Zhang W,Suzuiki K,Huang Y,Zhang P,Tang TS,Qu J,Yu Y,Liu GH,Qiao Jdoi
10.1007/s13238-019-0623-2subject
Has Abstractpub_date
2020-01-01 00:00:00pages
1-22issue
1eissn
1674-800Xissn
1674-8018pii
10.1007/s13238-019-0623-2journal_volume
11pub_type
杂志文章相关文献
Protein & Cell文献大全abstract::Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spec...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-020-00768-w
更新日期:2020-10-01 00:00:00
abstract::MicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central ...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-015-0168-y
更新日期:2015-07-01 00:00:00
abstract::A chimeric protein called Wallerian degeneration slow (Wld(S)) was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration. This provides a useful tool in elucidating the mechanisms of axon degeneration. Over-expression of Wld(S) attenuates the axon degeneration that is as...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-010-0021-2
更新日期:2010-03-01 00:00:00
abstract::Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body rad...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-014-0130-4
更新日期:2015-03-01 00:00:00
abstract::Treatment of latent tuberculosis infection remains an important goal of global TB eradication. To this end, targets that are essential for intracellular survival of Mycobacterium tuberculosis are particularly attractive. Arylamine N-acetyltransferase (NAT) represents such a target as it is, along with the enzymes enco...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-010-0037-7
更新日期:2010-04-01 00:00:00
abstract::Fanconi anemia (FA) is an autosomal or X-linked recessive disorder characterized by chromosomal instability, bone marrow failure, cancer susceptibility, and a profound sensitivity to agents that produce DNA interstrand cross-link (ICL). To date, 15 genes have been identified that, when mutated, result in FA or an FA-l...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-011-1098-y
更新日期:2011-09-01 00:00:00
abstract::Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans. One example is SARS, which caused a worldwide health threat in 2003. In coronaviruses, the structural protein N (nucleocapsid protein) associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial ...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-010-0079-x
更新日期:2010-07-01 00:00:00
abstract::Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry i...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-018-0521-z
更新日期:2019-03-01 00:00:00
abstract::Hannum and colleagues performed DNA methylation sequencing to examine the relationship between DNA methylome and aging rate. Notably, they succeeded in building a quantitative and reproducible model based on the epigenetic bio-markers to predict aging rate with high accuracy. This progress enlightens us in many aspect...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-013-3913-0
更新日期:2013-10-01 00:00:00
abstract::Vision formation is classically based on projections from retinal ganglion cells (RGC) to the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Neurons in the mouse V1 are tuned to light stimuli. Although the cellular information of the retina and the LGN has been widely studied, the transcriptome p...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-020-00720-y
更新日期:2020-06-01 00:00:00
abstract::We recently found that growth factor receptor-bound (Grb) protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit (CNGA1). Grb14 promotes the CNG channel closure through its Ras-associating (RA) domain. In the current study we show that this RA domain-media...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-011-1115-1
更新日期:2011-11-01 00:00:00
abstract::Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have been associated with amyotrophic lateral sclerosis (ALS). FUS-positive neuropathology is reported in a range of neurodegenerative diseases, including ALS and fronto-temporal lobar degeneration with ubiquitin-positive pathology (FTLDU). T...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-011-1014-5
更新日期:2011-02-01 00:00:00
abstract::Ultraviolet-B (UV-B) is a relatively minor component of sunlight, but can induce stress-related physiological processes or UV-B-specific photomorphogenic responses in plants. In the last decade, significant progress has been made in understanding the UV-B photomorphogenic pathway, including identification of the key c...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-013-3036-7
更新日期:2013-07-01 00:00:00
abstract::Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on co...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-010-0125-8
更新日期:2010-11-01 00:00:00
abstract::Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-020-00753-3
更新日期:2020-07-14 00:00:00
abstract::While the majority of all human cancers counteract telomere shortening by expressing telomerase, ~15% of all cancers maintain telomere length by a telomerase-independent mechanism known as alternative lengthening of telomeres (ALT). Here, we show that high load of intrinsic DNA damage is present in ALT cancer cells, l...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-019-0634-z
更新日期:2019-11-01 00:00:00
abstract::Therapeutic monoclonal antibodies are among the most effective biotherapeutics to date. An important aspect of antibodies is their ability to bind antigen while at the same time recruit immune effector functions. The majority of approved recombinant monoclonal antibody therapies are of the human IgG1 subclass, which c...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-017-0473-8
更新日期:2018-01-01 00:00:00
abstract::Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC popu...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-015-0140-x
更新日期:2015-04-01 00:00:00
abstract::Human embryonic stem cells (hESCs) depend on glycolysis for energy and substrates for biosynthesis. To understand the mechanisms governing the metabolism of hESCs, we investigated the transcriptional regulation of glucose transporter 1 (GLUT1, SLC2A1), a key glycolytic gene to maintain pluripotency. By combining the g...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-019-0637-9
更新日期:2019-09-01 00:00:00
abstract::Macroautophagy is an evolutionarily conserved intracellular degradation system used by life ranging from yeasts to mammals. The core autophagic machinery is composed of ATG (autophagy-related) protein constituents. One particular member of the ATG protein family, Atg7, has been the focus of recent research. Atg7 acts ...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-015-0195-8
更新日期:2015-10-01 00:00:00
abstract::The importance of NAC (named as NAM, ATAF1, 2, and CUC2) proteins in plant development, transcription regulation and regulatory pathways involving protein-protein interactions has been increasingly recognized. We report here the high resolution crystal structure of SNAC1 (stress-responsive NAC) NAC domain at 2.5 Å. Al...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-011-1010-9
更新日期:2011-01-01 00:00:00
abstract::CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibi...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-011-1089-z
更新日期:2011-09-01 00:00:00
abstract::Studies on chronic myeloid leukemia (CML) have served as a paradigm for cancer research and therapy. These studies involve the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It become...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-013-2115-0
更新日期:2013-03-01 00:00:00
abstract::Leukocyte immunoglobulin-like receptors (LILRs), also called CD85s, ILTs, or LIRs, are important mediators of immune activation and tolerance that contain tandem immunoglobulin (Ig)-like folds. There are 11 (in addition to two pseudogenes) LILRs in total, two with two Ig-like domains (D1D2) and the remaining nine with...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-013-3908-x
更新日期:2013-10-01 00:00:00
abstract::Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's disease, which makes most of cases. New researches indicate that gastrointestinal tract microbiota are directly linked to dementia pathogenesis through tri...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-016-0338-6
更新日期:2017-02-01 00:00:00
abstract::Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-012-2108-4
更新日期:2013-01-01 00:00:00
abstract::Siva-1, as a p53-inducible gene, has been shown to induce extensive apoptosis in a number of different cell lines. Recent evidence suggests that Siva-1 functions as a part of the auto-regulatory feedback loop that restrains p53 through facilitating Mdm2-mediated p53 degradation. Also, Siva-1 plays an important role in...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-012-2018-5
更新日期:2012-02-01 00:00:00
abstract::Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious k...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-015-0153-5
更新日期:2015-05-01 00:00:00
abstract::Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobacterium tuberculosis (Mtb). Consequently, stalling dehydration cures tuberculosis (TB). Clinically used anti-TB drugs like thiacetazone (TAC) and isoxyl (ISO) as well as flavonoids inhibit the enzyme activity o...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-015-0181-1
更新日期:2015-07-01 00:00:00
abstract::With the smooth move towards the coming expected clinical reports of anticancer pharmaceutical molecules targeting telomeres and telomerase, and also with the exciting success in the extension of lifespan by regulating telomerase activity without increased onset of oncogenesis in laboratory mouse models (Garcia-Cao et...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-013-3002-4
更新日期:2013-08-01 00:00:00