Abstract：
:Induced pluripotent stem cells (iPSCs) are generated via the expression of the transcription factors OCT4 (also known as POU5F1), SOX2, KLF4 and cMYC (OSKM) in somatic cells. In contrast to murine naive iPSCs, conventional human iPSCs are in a more developmentally advanced state called primed pluripotency. Here, we report that human naive iPSCs (niPSCs) can be generated directly from fewer than 1,000 primary human somatic cells, without requiring stable genetic manipulation, via the delivery of modified messenger RNAs using microfluidics. Expression of the OSKM factors in combination with NANOG for 12 days generates niPSCs that are free of transgenes, karyotypically normal and display transcriptional, epigenetic and metabolic features indicative of the naive state. Importantly, niPSCs efficiently differentiate into all three germ layers. While niPSCs can be generated at low frequency under conventional conditions, our microfluidics approach enables the robust and cost-effective production of patient-specific niPSCs for regenerative medicine applications, including disease modelling and drug screening.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Giulitti S,Pellegrini M,Zorzan I,Martini P,Gagliano O,Mutarelli M,Ziller MJ,Cacchiarelli D,Romualdi C,Elvassore N,Martello Gdoi
10.1038/s41556-018-0254-5subject
Has Abstractpub_date
2019-02-01 00:00:00pages
275-286issue
2eissn
1465-7392issn
1476-4679pii
10.1038/s41556-018-0254-5journal_volume
21pub_type
杂志文章abstract：:Mitochondrial function degenerates with ageing and in ageing-related neuromuscular degenerative diseases, causing physiological decline of the cell. Factors that can delay the degenerative process are actively sought after. Here, we show that reduced cytosolic protein synthesis is a robust cellular strategy that suppr...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1769
更新日期：2008-09-01 00:00:00
abstract：:The initial differential treatment of the two X chromosomes during X-chromosome inactivation is controlled by the X-inactivation centre (Xic). This locus determines how many X chromosomes are present in a cell ('counting') and which X chromosome will be inactivated in female cells ('choice'). Critical control sequence...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1365
更新日期：2006-03-01 00:00:00
abstract：:During cell division, many animal cells transform into a spherical shape and assemble a contractile ring composed of actin filaments and myosin motors at the equator to separate the cell body into two. Although actomyosin regulatory proteins are spatio-temporally controlled during cytokinesis, the direct contribution ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3142
更新日期：2015-04-01 00:00:00
abstract：:Science denial is not new but, in the digital age, evidence-based conclusions appear to be increasingly threatened by beliefs based on emotion and isolated personal experience. When confronting a post-truth world, scientists must defend the scientific method and increase public engagement. ...
journal_title：Nature cell biology
pub_type： 社论
doi：10.1038/s41556-018-0231-z
更新日期：2018-11-01 00:00:00
abstract：:The kinase AMPK, a sensor of cellular energy stress, has been shown to oppose the growth-promoting activity of YAP, the transcriptional co-activator downstream of the Hippo signalling pathway. This finding may help to explain why the antidiabetic drug metformin, for which AMPK is a key effector, is linked to cancer-pr...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3141
更新日期：2015-04-01 00:00:00
abstract：:Cellular senescence is a tumour suppressor programme characterized by a stable cell cycle arrest. Here we report that cellular senescence triggered by a variety of stimuli leads to diminished ribosome biogenesis and the accumulation of both rRNA precursors and ribosomal proteins. These defects were associated with red...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-018-0127-y
更新日期：2018-07-01 00:00:00
abstract：:Spatial and temporal coordination of polo-like kinase 1 (Plk1) activity is necessary for mitosis and cytokinesis, and this is achieved through binding to phosphorylated docking proteins with distinct subcellular localizations. Although cyclin-dependent kinase 1 (Cdk1) creates these phosphorylated docking sites in meta...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1557
更新日期：2007-04-01 00:00:00
abstract：:Extracellular signal regulated kinases (ERKs) represent a signalling hub in many physiological responses and have pivotal functions in cell proliferation, differentiation, development and death, as well as in synaptic plasticity. Mitogen-activated protein kinase phosphatases (MKPs) selectively inactivate ERKs by depho...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1447
更新日期：2006-08-01 00:00:00
abstract：:The guanosine tri-phosphatase Ran stimulates assembly of microtubule spindles. However, it is not known what aspects of the microtubule cytoskeleton are subject to regulation by Ran in mitosis. Here we show that Ran-GTP stimulates microtubule assembly by increasing the rescue frequency of microtubules three- to eightf...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35060000
更新日期：2001-03-01 00:00:00
abstract：:Clathrin-mediated endocytosis is independent of actin dynamics in many circumstances but requires actin polymerization in others. We show that membrane tension determines the actin dependence of clathrin-coat assembly. As found previously, clathrin assembly supports formation of mature coated pits in the absence of ac...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2307
更新日期：2011-08-14 00:00:00
abstract：:Cell-cell adhesion mediated by specific cell-surface molecules is essential for multicellular development. Here we quantify de-adhesion forces at the resolution of individual cell-adhesion molecules, by controlling the interactions between single cells and combining single-molecule force spectroscopy with genetic mani...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35014000
更新日期：2000-06-01 00:00:00
abstract：:Here we show that human Zeste White 10 (Zw10) and Rough deal (Rod) are new components of the mitotic checkpoint, as cells lacking these proteins at kinetochores fail to arrest in mitosis when exposed to microtubule inhibitors. Checkpoint failure and premature mitotic exit may explain why cells defective for hZw10 and ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35046598
更新日期：2000-12-01 00:00:00
abstract：:Compartmentalization has long been known to have a key role in regulation of cellular processes. By keeping enzymes and regulatory complexes in compartments where the delivery of substrate or exit of product is controlled, competing reactions can occur simultaneously in different parts of the cell. Moreover, spatial c...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/35014078
更新日期：2000-06-01 00:00:00
abstract：:The spindle assembly checkpoint (SAC) is a unique signalling mechanism that responds to the state of attachment of the kinetochore to spindle microtubules. SAC signalling is activated by unattached kinetochores, and it is silenced after these kinetochores form end-on microtubule attachments. Although the biochemical c...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3179
更新日期：2015-07-01 00:00:00
abstract：:Unrepaired DNA double-strand breaks (DSBs) cause genetic instability that leads to malignant transformation or cell death. Cells respond to DSBs with the ordered recruitment of signalling and repair proteins to the site of lesion. Protein modification with ubiquitin is crucial for the signalling cascade, but how ubiqu...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2367
更新日期：2011-10-23 00:00:00
abstract：:SLC7A11-mediated cystine uptake is critical for maintaining redox balance and cell survival. Here we show that this comes at a significant cost for cancer cells with high levels of SLC7A11. Actively importing cystine is potentially toxic due to its low solubility, forcing cancer cells with high levels of SLC7A11 (SLC7...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-020-0496-x
更新日期：2020-04-01 00:00:00
abstract：:Store-operated Ca(2+) channels (SOCs) are activated in response to Ca(2+) release from the endoplasmic reticulum (ER). The stromal interaction molecule 1 (STIM1) is the ER sensor that transmits the stored Ca(2+) content to the pore-forming SOCs Orai and TRPC channels. Recent studies reveal high levels of Orai1 and STI...
journal_title：Nature cell biology
pub_type： 新闻
doi：10.1038/ncb0608-639
更新日期：2008-06-01 00:00:00
abstract：:Topoisomerase II (Topo II) is required to separate intertwined sister chromatids before chromosome segregation can occur in mitosis. However, it remains to be resolved whether Topo II has any role in checkpoint control. Here we report that when phosphorylated, Ser 1524 of Topo IIalpha acts as a binding site for the BR...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1828
更新日期：2009-02-01 00:00:00
abstract：:Gastrulation leads to three germ layers--ectoderm, mesoderm and endoderm--that are separated by two basement membranes. In the mouse embryo, the emergent gut endoderm results from the widespread intercalation of cells of two distinct origins: pluripotent epiblast-derived definitive endoderm (DE) and extra-embryonic vi...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3070
更新日期：2014-12-01 00:00:00
abstract：:Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism a...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3575
更新日期：2017-09-01 00:00:00
abstract：:The promyelocytic leukaemia (PML) tumour-suppressor protein potentiates p53 function by regulating post-translational modifications, such as CBP-dependent acetylation and Chk2-dependent phosphorylation, in the PML-Nuclear Body (NB). PML was recently shown to interact with the p53 ubiquitin-ligase Mdm2 (refs 4-6); howe...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1147
更新日期：2004-07-01 00:00:00
abstract：:Lingual keratinized epithelial cells, which constitute the filiform papillae of the tongue, have one of the most rapid tissue turnover rates in the mammalian body and are thought to be the source of squamous cell carcinoma of the tongue. However, the mechanism of tissue maintenance and regeneration is largely unknown ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2719
更新日期：2013-05-01 00:00:00
abstract：:Individual neurons form specific elaborate dendritic structures that receive presynaptic information. The pattern of dendritic branching is regulated by the microtubule-associated motor protein dynein, which is responsible for the transport of essential endosomes and other organelles into the dendrites. ...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb1008-1131
更新日期：2008-10-01 00:00:00
abstract：:Cancer cells consume large quantities of glucose and primarily use glycolysis for ATP production, even in the presence of adequate oxygen. This metabolic signature (aerobic glycolysis or the Warburg effect) enables cancer cells to direct glucose to biosynthesis, supporting their rapid growth and proliferation. However...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2172
更新日期：2011-03-01 00:00:00
abstract：:Osteoclasts are multinucleated cells of the monocyte/macrophage lineage that degrade bone. Here, we used lineage tracing studies-labelling cells expressing Cx3cr1, Csf1r or Flt3-to identify the precursors of osteoclasts in mice. We identified an erythromyeloid progenitor (EMP)-derived osteoclast precursor population. ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0437-8
更新日期：2020-01-01 00:00:00
abstract：:Mammalian telomeres consist of non-coding TTAGGG repeats that are bound by the multi-protein complex 'shelterin', thus protecting chromosome ends from DNA repair mechanisms and degradation. Mammalian telomeric chromatin is enriched for the constitutive heterochromatin marks H3K9me3, H4K20me3 and HP1 (refs 2, 3, 4, 5, ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1685
更新日期：2008-02-01 00:00:00
abstract：:Wiskott-Aldrich syndrome protein (WASP) and N-WASP have emerged as key proteins connecting signalling cascades to actin polymerization. Here we show that the amino-terminal WH1 domain, and not the polyproline-rich region, of N-WASP is responsible for its recruitment to sites of actin polymerization during Cdc42-indepe...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35017080
更新日期：2000-07-01 00:00:00
abstract：:Humans suffer from high rates of fetal aneuploidy, often arising from the absence of meiotic crossover recombination between homologous chromosomes. Meiotic recombination is initiated by double-strand breaks (DSBs) generated by the SPO11 transesterase. In yeast and worms, at least one buffering mechanism, crossover ho...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2451
更新日期：2012-03-04 00:00:00
abstract：:Formation of a stable lamellipodium at the front of migrating cells requires localization of Rac activation to the leading edge. Restriction of alpha4 integrin phosphorylation to the leading edge limits the interaction of alpha4 with paxillin to the sides and rear of a migrating cell. The alpha4-paxillin complex inhib...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1234
更新日期：2005-04-01 00:00:00
abstract：:Once considered to be contained, infectious diseases of bacterial origin are now making a comeback. A lack of innovative therapies and the appearance of drug-resistant pathogens are becoming increasingly serious problems. A better understanding of pathogen-host interactions at the cellular and molecular levels is nece...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/15620
更新日期：1999-11-01 00:00:00
