Abstract:
:Human pluripotent stem cells (hPSCs) are an important system to study early human development, model human diseases, and develop cell replacement therapies. However, genetic manipulation of hPSCs is challenging and a method to simultaneously activate multiple genomic sites in a controllable manner is sorely needed. Here, we constructed a CRISPR-ON system to efficiently upregulate endogenous genes in hPSCs. A doxycycline (Dox) inducible dCas9-VP64-p65-Rta (dCas9-VPR) transcription activator and a reverse Tet transactivator (rtTA) expression cassette were knocked into the two alleles of the AAVS1 locus to generate an iVPR hESC line. We showed that the dCas9-VPR level could be precisely and reversibly controlled by the addition and withdrawal of Dox. Upon transfection of multiplexed gRNA plasmid targeting the NANOG promoter and Dox induction, we were able to control NANOG gene expression from its endogenous locus. Interestingly, an elevated NANOG level promoted naïve pluripotent gene expression, enhanced cell survival and clonogenicity, and enabled hESCs to integrate with the inner cell mass (ICM) of mouse blastocysts in vitro. Thus, iVPR cells provide a convenient platform for gene function studies as well as high-throughput screens in hPSCs.
journal_name
Protein Celljournal_title
Protein & cellauthors
Guo J,Ma D,Huang R,Ming J,Ye M,Kee K,Xie Z,Na Jdoi
10.1007/s13238-016-0360-8subject
Has Abstractpub_date
2017-05-01 00:00:00pages
379-393issue
5eissn
1674-800Xissn
1674-8018pii
10.1007/s13238-016-0360-8journal_volume
8pub_type
杂志文章相关文献
Protein & Cell文献大全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::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::S-Nitros(yl)ation is a ubiquitous redox-based post-translational modification of protein cysteine thiols by nitric oxide or its derivatives, which transduces the bioactivity of nitric oxide (NO) by regulation of protein conformation, activity, stability, localization and protein-protein interactions. These years, more...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-012-2094-6
更新日期:2012-12-01 00:00:00
abstract::Progranulin (PGRN) is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors (TNFR) and has therapeutic effects in inflammatory arthritis (Tang et. al,...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-015-0213-x
更新日期:2015-11-01 00:00:00
abstract::Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. Wit...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-016-0368-0
更新日期:2017-05-01 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::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::Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to ...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-019-00676-8
更新日期:2020-02-01 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::Flea-borne transmission is a recent evolutionary adaptation that distinguishes the deadly Yersinia pestis from its progenitor Y. Pseudotuberculosis, a mild pathogen transmitted via the food-borne route. Y. Pestis synthesizes biofilms in the flea gut, which is important for fleaborne transmission. Yersinia biofilms are...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-011-1024-3
更新日期:2011-03-01 00:00:00
abstract::The human Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor 1-like (Efl1), to promote the release of eukaryotic initiation factor 6 (eIF6...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-015-0242-5
更新日期:2016-03-01 00:00:00
abstract::The fruit fly, Drosophila melanogaster, is able to discriminate visual landmarks and form visual long-term memory in a flight simulator. Studies focused on the molecular mechanism of long-term memory have shown that memory formation requires mRNA transcription and protein synthesis. However, little is known about the ...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-011-1019-0
更新日期:2011-03-01 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::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::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::Histone deacetylase 6 (HDAC6), a predominantly cytoplasmic protein deacetylase, participates in a wide range of cellular processes through its deacetylase activity. However, the diverse functions of HDAC6 cannot be fully elucidated with its known substrates. In an attempt to explore the substrate diversity of HDAC6, w...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-014-0102-8
更新日期:2015-01-01 00:00:00
abstract::Sometimes crystals cannot diffract X-rays beyond 3.0 Å resolution due to the intrinsic flexibility associated with the protein. Low resolution diffraction data not only pose a challenge to structure determination, but also hamper interpretation of mechanistic details. Crystals of a 25.6 kDa non-Pfam, hypothetical prot...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-010-0045-7
更新日期:2010-05-01 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::Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datase...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-016-0342-x
更新日期:2017-02-01 00:00:00
abstract::Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-019-0608-1
更新日期:2019-04-01 00:00:00
abstract::In the original publication the PDB numbers were not cited. ...
journal_title:Protein & cell
pub_type: 已发布勘误
doi:10.1007/s13238-019-0619-y
更新日期:2019-07-01 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
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::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::While human induced pluripotent stem cells (hiPSCs) have promising applications in regenerative medicine, most of the hiPSC lines available today are not suitable for clinical applications due to contamination with nonhuman materials, such as sialic acid, and potential pathogens from animal-product-containing cell cul...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-012-2002-0
更新日期:2012-01-01 00:00:00
abstract::The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogeni...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-016-0320-3
更新日期:2016-11-01 00:00:00
abstract::This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and melanoma. We show that ERK5 expression is abundant in human lung cancer samples, and elevated ERK5 expression in lung cancer was linked to the acqu...
journal_title:Protein & cell
pub_type: 杂志文章
doi:10.1007/s13238-020-00701-1
更新日期:2020-11-01 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::T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The s...
journal_title:Protein & cell
pub_type: 杂志文章,评审
doi:10.1007/s13238-016-0367-1
更新日期:2018-03-01 00:00:00