Abstract:
:Brief expression of pluripotency-associated factors such as Oct4, Klf4, Sox2 and c-Myc (OKSM), in combination with differentiation-inducing signals, has been reported to trigger transdifferentiation of fibroblasts into other cell types. Here we show that OKSM expression in mouse fibroblasts gives rise to both induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) under conditions previously shown to induce only iNSCs. Fibroblast-derived iNSC colonies silenced retroviral transgenes and reactivated silenced X chromosomes, both hallmarks of pluripotent stem cells. Moreover, lineage tracing with an Oct4-CreER labeling system demonstrated that virtually all iNSC colonies originated from cells transiently expressing Oct4, whereas ablation of Oct4(+) cells prevented iNSC formation. Lastly, an alternative transdifferentiation cocktail that lacks Oct4 and was reportedly unable to support induced pluripotency yielded iPSCs and iNSCs carrying the Oct4-CreER-derived lineage label. Together, these data suggest that iNSC generation from fibroblasts using OKSM and other pluripotency-related reprogramming factors requires passage through a transient iPSC state.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Bar-Nur O,Verheul C,Sommer AG,Brumbaugh J,Schwarz BA,Lipchina I,Huebner AJ,Mostoslavsky G,Hochedlinger Kdoi
10.1038/nbt.3247subject
Has Abstractpub_date
2015-07-01 00:00:00pages
761-8issue
7eissn
1087-0156issn
1546-1696pii
nbt.3247journal_volume
33pub_type
杂志文章abstract::Pollen-mediated movement of transgenes from transplastomic oilseed rape (Brassica napus) into wild relatives will be avoided if chloroplasts are maternally transmitted. We assess the probability of chloroplast exchange between conventional oilseed rape and wild Brassica rapa to model the future behavior of transplasto...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/7952
更新日期:1999-04-01 00:00:00
abstract::Directed molecular evolution was applied to generate Cre recombinase variants that recognize a new DNA target sequence. Cre was adapted in a three-stage strategy to evolve recombinases to specifically recombine the new site. This complex multicycle task was made feasible by an improved directed-evolution procedure tha...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1101-1047
更新日期:2001-11-01 00:00:00
abstract::Proviruses carrying drug-inducible Oct4, Sox2, Klf4 and c-Myc used to derive 'primary' induced pluripotent stem (iPS) cells were segregated through germline transmission, generating mice and cells carrying subsets of the reprogramming factors. Drug treatment produced 'secondary' iPS cells only when the missing factor ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1520
更新日期:2009-02-01 00:00:00
abstract::Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current technologies have limited sensitivity or throughput. Here we present an approach to precisely and rapidly measure growth rates of many individual cells simultaneously. We flow cells in suspen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3666
更新日期:2016-10-01 00:00:00
abstract::Wild relatives of crops are an important source of genetic diversity for agriculture, but their gene repertoire remains largely unexplored. We report the establishment and analysis of a pan-genome of Glycine soja, the wild relative of cultivated soybean Glycine max, by sequencing and de novo assembly of seven phylogen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2979
更新日期:2014-10-01 00:00:00
abstract::Centromeric variation has been linked to cancer and infertility, but centromere sequences contain multiple tandem repeats and can only be assembled manually from long error-prone reads. Here we describe the centroFlye algorithm for centromere assembly using long error-prone reads, and apply it to assemble human centro...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-020-0582-4
更新日期:2020-11-01 00:00:00
abstract::Transcriptional silencing, one of the major impediments to gene therapy in humans, is often accompanied by replication during late S-phase. We report that transcriptional silencing and late replication were prevented by DNA sequences that can initiate DNA replication (replicators). When replicators were included in si...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1202
更新日期:2006-05-01 00:00:00
abstract::Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synth...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1259
更新日期:2006-11-01 00:00:00
abstract::Detection of mutations and damaged DNA bases is important for the early diagnosis of genetic disease. Here we describe an electrocatalytic method for the detection of single-base mismatches as well as DNA base lesions in fully hybridized duplexes, based on charge transport through DNA films. Gold electrodes modified w...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/80301
更新日期:2000-10-01 00:00:00
abstract::Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of plac...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4297
更新日期:2018-11-19 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature biotechnology
pub_type: 已发布勘误
doi:10.1038/s41587-019-0167-2
更新日期:2019-07-01 00:00:00
abstract::We describe a novel sequencing approach that combines non-gel-based signature sequencing with in vitro cloning of millions of templates on separate 5 microm diameter microbeads. After constructing a microbead library of DNA templates by in vitro cloning, we assembled a planar array of a million template-containing mic...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/76469
更新日期:2000-06-01 00:00:00
abstract::The identification of co-regulated genes and their transcription-factor binding sites (TFBS) are key steps toward understanding transcription regulation. In addition to effective laboratory assays, various computational approaches for the detection of TFBS in promoter regions of coexpressed genes have been developed. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt802
更新日期:2003-04-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is an essential regulator of normal and abnormal blood vessel growth. A monoclonal antibody (mAb) that targets VEGF suppresses tumor growth in murine cancer models and human patients. We investigated cellular and molecular events that mediate refractoriness of tumors to anti-a...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1323
更新日期:2007-08-01 00:00:00
abstract::Disease resistance (R) genes from wild relatives could be used to engineer broad-spectrum resistance in domesticated crops. We combined association genetics with R gene enrichment sequencing (AgRenSeq) to exploit pan-genome variation in wild diploid wheat and rapidly clone four stem rust resistance genes. AgRenSeq ena...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-018-0007-9
更新日期:2019-02-01 00:00:00
abstract::Debates on patenting DNA must evolve to reflect the global decline in filings and regional disparities in patenting activity. ...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt0207-185
更新日期:2007-02-01 00:00:00
abstract::CD4 functions as a major T-cell surface receptor for human immunodeficiency virus by binding the human immunodeficiency virus type 1 (HIV-1) envelope protein gp120 with relatively high affinity. We have developed constrained aromatically modified analogs of the secondary structures of the first domain of CD4 in order ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0297-150
更新日期:1997-02-01 00:00:00
abstract::Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we presen...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3350
更新日期:2015-10-01 00:00:00
abstract::Can new approaches for deriving human stem cells circumnavigate existing patents that dominate embryonic stem cell intellectual property? ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0406-411
更新日期:2006-04-01 00:00:00
abstract::Nitrile hydratase (NHase), which catalyzes the hydration of nitriles to amides, has been used in the industrial production of acrylamide and nicotinamide. Recent studies on NHases, which are roughly classified into iron and cobalt types according to the metal involved, have clarified the photoactivation mechanism, the...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt0898-733
更新日期:1998-08-01 00:00:00
abstract::By using an engineered, self-assembling, proteinaceous, 2-nm pore equipped with a metal-actuated switch, a technique to reversibly permeabilize the plasma membrane to small molecules (approximately 1000 Da) has been developed. We have demonstrated the dose-dependent permeabilization of fibroblasts by pores designed to...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0397-278
更新日期:1997-03-01 00:00:00
abstract::Linear, medium-chain (C8-C12) hydrocarbons are important components of fuels as well as commodity and specialty chemicals. As industrial microbes do not contain pathways to produce medium-chain chemicals, approaches such as overexpression of endogenous enzymes or deletion of competing pathways are not available to the...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt.4022
更新日期:2017-12-01 00:00:00
abstract::We introduce Sailfish, a computational method for quantifying the abundance of previously annotated RNA isoforms from RNA-seq data. Because Sailfish entirely avoids mapping reads, a time-consuming step in all current methods, it provides quantification estimates much faster than do existing approaches (typically 20 ti...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2862
更新日期:2014-05-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature biotechnology
pub_type: 已发布勘误
doi:10.1038/s41587-019-0253-5
更新日期:2019-09-01 00:00:00
abstract::Droplet single-cell RNA-sequencing (dscRNA-seq) has enabled rapid, massively parallel profiling of transcriptomes. However, assessing differential expression across multiple individuals has been hampered by inefficient sample processing and technical batch effects. Here we describe a computational tool, demuxlet, that...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4042
更新日期:2018-01-01 00:00:00
abstract::The human genome encodes approximately 100,000 different genes, and at least partial sequence information for nearly all will be available soon. Sequence information alone, however, is insufficient for a full understanding of gene function, expression, regulation, and splice-site variation. Because cellular processes ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1296-1675
更新日期:1996-12-01 00:00:00
abstract::We have developed a generic procedure to purify proteins expressed at their natural level under native conditions using a novel tandem affinity purification (TAP) tag. The TAP tag allows the rapid purification of complexes from a relatively small number of cells without prior knowledge of the complex composition, acti...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/13732
更新日期:1999-10-01 00:00:00
abstract::Many promising targets for T-cell-based cancer immunotherapies are self-antigens. During thymic selection, T cells bearing T cell receptors (TCRs) with high affinity for self-antigen are eliminated. The affinity of the remaining low-avidity TCRs can be improved to increase their antitumor efficacy, but conventional sa...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4004
更新日期:2017-12-01 00:00:00
abstract::Glycoprotein hormones are noncovalent heterodimers comprised of a common alpha subunit and a hormone-specific beta subunit. Secretion and biologic action of these hormones are dependent on the formation of the heterodimer. The human LH beta subunit is unique among the other beta subunits in that it assembles inefficie...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0797-663
更新日期:1997-07-01 00:00:00
abstract::A human pancreatic beta-cell line that is functionally equivalent to primary beta-cells has not been available. We established a reversibly immortalized human beta-cell clone (NAKT-15) by transfection of primary human beta-cells with a retroviral vector containing simian virus 40 large T-antigen (SV40T) and human telo...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1145
更新日期:2005-10-01 00:00:00