Abstract:
:For reasons that are unclear the production of embryonic stem cells from ungulates has proved elusive. Here, we describe induced pluripotent stem cells (iPSC) derived from porcine fetal fibroblasts by lentiviral transduction of 4 human (h) genes, hOCT4, hSOX2, hKLF4, and hc-MYC, the combination commonly used to create iPSC in mouse and human. Cells were cultured on irradiated mouse embryonic fibroblasts (MEF) and in medium supplemented with knockout serum replacement and FGF2. Compact colonies of alkaline phosphatase-positive cells emerged after approximately 22 days, providing an overall reprogramming efficiency of approximately 0.1%. The cells expressed porcine OCT4, NANOG, and SOX2 and had high telomerase activity, but also continued to express the 4 human transgenes. Unlike human ESC, the porcine iPSC (piPSC) were positive for SSEA-1, but negative for SSEA-3 and -4. Transcriptional profiling on Affymetrix (porcine) microarrays and real time RT-PCR supported the conclusion that reprogramming to pluripotency was complete. One cell line, ID6, had a normal karyotype, a cell doubling time of approximately 17 h, and has been maintained through >220 doublings. The ID6 line formed embryoid bodies, expressing genes representing all 3 germ layers when cultured under differentiating conditions, and teratomas containing tissues of ectoderm, mesoderm, and endoderm origin in nude mice. We conclude that porcine somatic cells can be reprogrammed to form piPSC. Such cell lines derived from individual animals could provide a means for testing the safety and efficacy of stem cell-derived tissue grafts when returned to the same pigs at a later age.
journal_name
Proc Natl Acad Sci U S Aauthors
Ezashi T,Telugu BP,Alexenko AP,Sachdev S,Sinha S,Roberts RMdoi
10.1073/pnas.0905284106subject
Has Abstractpub_date
2009-07-07 00:00:00pages
10993-8issue
27eissn
0027-8424issn
1091-6490pii
0905284106journal_volume
106pub_type
杂志文章abstract::gC1qR is one of the C1q receptors implicated in the regulation of innate and adaptive immunity. We found that gC1qR inhibits RIG-I and MDA5-dependent antiviral signaling. Double stranded RNA and virus trigger the translocation of gC1qR to the mitochondrial outer membrane leading to the interaction of gC1qR with the RI...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0811029106
更新日期:2009-02-03 00:00:00
abstract::The second critical endpoint in the basalt-H(2)O system was directly determined by a high-pressure and high-temperature X-ray radiography technique. We found that the second critical endpoint occurs at around 3.4 GPa and 770 °C (corresponding to a depth of approximately 100 km in a subducting slab), which is much shal...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1010968108
更新日期:2011-05-17 00:00:00
abstract::With 13C NMR, phosphoglucose isomerase (PGI; D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9) is shown to produce mannose 6-phosphate (M6P) slowly from a much more rapidly catalyzed equilibrium between glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P). The identity of M6P and its formation from G6P plus F6P a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.4.1237
更新日期:1993-02-15 00:00:00
abstract::Although advances in microfluidic technology have enabled increasingly sophisticated biosensing and bioassay operations to be performed at the microscale, many of these applications employ such small amounts of charged biomolecules (DNA, proteins, and peptides) that they must first be preconcentrated to a detectable l...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0506848103
更新日期:2006-03-28 00:00:00
abstract::Reef-building corals are critically important species that are threatened by anthropogenic stresses including climate change. In attempts to understand corals' responses to stress and other aspects of their biology, numerous genomic and transcriptomic studies have been performed, generating a variety of hypotheses abo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1722151115
更新日期:2018-05-15 00:00:00
abstract::Studies of prostate cancer pathogenesis and development of new therapies have been hampered by a lack of appropriate mouse models. We have generated PSA-Cre-ER(T2) mice that express the tamoxifen-dependent Cre-ER(T2) recombinase selectively in prostatic epithelium, thus allowing us to target floxed genes selectively i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0712021105
更新日期:2008-02-19 00:00:00
abstract::Experimental allergic encephalomyelitis (EAE), an autoimmune model of multiple sclerosis, is a complex disease influenced by genetic, intrinsic, and environmental factors. In this study, we questioned whether parent-of-origin effects influence EAE, using reciprocal F2 intercross progeny generated between EAE-susceptib...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0600536103
更新日期:2006-05-23 00:00:00
abstract::The anti-inflammatory activity of intravenous Ig (IVIG) results from a minor population of the pooled IgG molecules that contains terminal alpha2,6-sialic acid linkages on their Fc-linked glycans. These anti-inflammatory properties can be recapitulated with a fully recombinant preparation of appropriately sialylated I...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0810163105
更新日期:2008-12-16 00:00:00
abstract::The 2012-2015 drought has left California with severely reduced snowpack, soil moisture, ground water, and reservoir stocks, but the impact of this estimated millennial-scale event on forest health is unknown. We used airborne laser-guided spectroscopy and satellite-based models to assess losses in canopy water conten...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1523397113
更新日期:2016-01-12 00:00:00
abstract::Mycobacterium abscessus (Mabs) is a rapidly growing Mycobacterium and an emerging pathogen in humans. Transitioning from a smooth (S) high-glycopeptidolipid (GPL) producer to a rough (R) low-GPL producer is associated with increased virulence in zebrafish, which involves the formation of massive serpentine cords, absc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1605477113
更新日期:2016-07-19 00:00:00
abstract::Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1319313110
更新日期:2013-12-03 00:00:00
abstract::Ten eleven translocation (TET) enzymes (TET1/TET2/TET3) and thymine DNA glycosylase (TDG) play crucial roles in early embryonic and germ cell development by mediating DNA demethylation. However, the molecular mechanisms that regulate TETs/TDG expression and their role in cellular differentiation, including that of the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1317397110
更新日期:2013-10-29 00:00:00
abstract::The proinflammatory and catabolic cytokine IL-1β has been implicated in the pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and cartilage degeneration. Although synovial macrophages are suggested to be the source of IL-1β, the mechanism remains unclear. Ectopic deposition of hydroxyapatite (HA) ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1111101108
更新日期:2011-09-06 00:00:00
abstract::A molecular dynamics simulation of the gramicidin A channel in an explicit dimyristoyl phosphatidylcholine bilayer was generated to study the details of lipid-protein interactions at the microscopic level. Solid-state NMR properties of the channel averaged over the 500-psec trajectory are in excellent agreement with a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.24.11631
更新日期:1994-11-22 00:00:00
abstract::Diabetes is now the most common cause of progressive kidney failure leading to dialysis or transplantation. The central pathological feature of diabetic nephropathy is accumulation of extracellular matrix within the glomeruli. The factors in the diabetic milieu responsible for extracellular matrix accumulation are not...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.5.1814
更新日期:1993-03-01 00:00:00
abstract::Proofreading mechanisms increase specificity in biochemical reactions by allowing for the dissociation of intermediate complexes. These mechanisms disrupt and reset the reaction to undo errors at the cost of increased time of reaction and free energy expenditure. Here, we draw an analogy between proofreading and micro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1119911109
更新日期:2012-07-24 00:00:00
abstract::In over 90% of cervical cancers and cancer-derived cell lines, the p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV). The HPV E6 protein promotes the degradation of p53 and thus inhibits the stabilization and activation of p53 that would normally occur in response to HPV E7 oncogene expression. R...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.15.8501
更新日期:2000-07-18 00:00:00
abstract::Seasonal variations in the properties of rabbit-liver fructose 1,6-bisphosphatase have now been linked to corresponding changes in the levels of proteolytic activity in the liver extracts. Incubation of native fructose 1,6-bisphosphatase with purified liver lysosomes causes a 3-fold increase in catalytic activity at p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.2.303
更新日期:1973-02-01 00:00:00
abstract::As a master regulator of functional Ig heavy chain (IgH) expression, the IgH 3' regulatory region (3'RR) controls multiple transcription events at various stages of B-cell ontogeny, from newly formed B cells until the ultimate plasma cell stage. The IgH 3'RR plays a pivotal role in early B-cell receptor expression, ge...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1514090113
更新日期:2016-02-09 00:00:00
abstract::The RNA synthesized in vitro by the virion-associated RNA-instructed RNA polymerase of purified vesicular stomatitis virus contains polyadenylate sequences. These have been demonstrated by their partial resistance to pancreatic and T(1) ribonucleases and their capacity to bind to poly(U) filters and oligo(dT)-cellulos...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.70.12.3566
更新日期:1973-12-01 00:00:00
abstract::An unsaturated fatty acid-requiring mutant derived from Chinese hamster ovary (CHO) cells has been isolated and characterized. This mutant grows normally when oleate or other unsaturated fatty acids are supplemented in the growth medium. Unlike the wild-type CHO cells, growth stops when medium is deprived of unsaturat...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.1.24
更新日期:1976-01-01 00:00:00
abstract::The reproductive activity of Trypanosoma lewisi was strikingly enhanced and sometimes prolonged for 2 days when sublethal doses of adenine were given to rats. The drug was effective when given for 5 or 7 days in the diet and/or intraperitoneally, starting one or two days before infection through two days after infecti...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.1.1
更新日期:1971-01-01 00:00:00
abstract::Synaptic competition is a basic feature of developing neural connections. To shed light on its dependence on the activity pattern of competing inputs, we investigated in vivo rat motoneuronal firing during late embryonic and early neonatal life, when synapse elimination occurs in muscle. Electromyographic recordings w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.202471199
更新日期:2002-10-01 00:00:00
abstract::The convulsant agent methionine sulfoximine inhibits brain glutamine synthetase irreversibly and the inhibitor becomes bound to the active site of the enzyme as methionine sulfoximine phosphate. Only one of the four isomers of methionine sulfoximine, L-methionine-S-sulfoximine, inhibits glutamine synthetase. In the pr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.66.2.500
更新日期:1970-06-01 00:00:00
abstract::Intrathymic T-cell development requires temporally regulated rearrangement and expression of T-cell receptor (TCR) genes. To assess the role of the TCR beta gene transcriptional enhancer (Ebeta) in this process, mouse strains in which Ebeta is deleted were generated using homologous recombination techniques. We report...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.15.7877
更新日期:1996-07-23 00:00:00
abstract::The ability to control drops and their movements on phobic surfaces is important in printing or patterning, microfluidic devices, and water-repellent materials. These materials are always micro-/nanotextured, and a natural limitation of repellency occurs when drops are small enough (as in a dew) to get trapped in the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1506874112
更新日期:2015-07-28 00:00:00
abstract::DNA sequences containing short adenine tracts are intrinsically curved and play a role in transcriptional regulation. Despite many high-resolution NMR and x-ray studies, the origins of curvature remain disputed. Long-range restraints provided by 85 residual dipolar couplings were measured for a DNA decamer containing ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0437877100
更新日期:2003-03-04 00:00:00
abstract::Representational difference analysis was used to search for pathogens in multiple sclerosis brains. We detected a 341-nucleotide fragment that was 99.4% identical to the major DNA binding protein gene of human herpesvirus 6 (HHV-6). Examination of 86 brain specimens by PCR demonstrated that HHV-6 was present in > 70% ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.92.16.7440
更新日期:1995-08-01 00:00:00
abstract::An invariant substructure that forms two interlocked pairs of neighboring beta-strands occurs in essentially all known sandwich-like proteins. Eight conserved positions in these strands were recently shown to act as structural determinants. To test whether the residues at these invariant positions are conserved for me...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501038102
更新日期:2005-03-15 00:00:00
abstract::Human malignant pleural mesothelioma (MPM) is considered a rare tumor, but recent estimations indicate that one-quarter million people will die of this neoplasm in Europe in the next three decades. The mineral asbestos is considered the main causative agent of this neoplasm. MPM is largely unresponsive to conventional...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1213238109
更新日期:2012-10-30 00:00:00