Abstract:
:One goal of regenerative medicine, to use stem cells to replace cells lost by injury or disease, depends on producing an excess of the relevant cell for study or transplantation. To this end, the stepwise differentiation of stem cells into specialized derivatives has been successful for some cell types, but a major problem remains the inefficient conversion of cells from one stage of differentiation to the next. If specialized cells are to be produced in large numbers it will be necessary to expand progenitor cells, without differentiation, at some steps of the process. Using the pancreatic lineage as a model for embryonic-stem-cell differentiation, we demonstrate that this is a solvable problem. Co-culture with organ-matched mesenchyme permits proliferation and self-renewal of progenitors, without differentiation, and enables an expansion of more than a million-fold for human endodermal cells with full retention of their developmental potential. This effect is specific both to the mesenchymal cell and to the progenitor being amplified. Progenitors that have been serially expanded on mesenchyme give rise to glucose-sensing, insulin-secreting cells when transplanted in vivo. Theoretically, the identification of stage-specific renewal signals can be incorporated into any scheme for the efficient production of large numbers of differentiated cells from stem cells and may therefore have wide application in regenerative biology.
journal_name
Naturejournal_title
Natureauthors
Sneddon JB,Borowiak M,Melton DAdoi
10.1038/nature11463subject
Has Abstractpub_date
2012-11-29 00:00:00pages
765-8issue
7426eissn
0028-0836issn
1476-4687pii
nature11463journal_volume
491pub_type
杂志文章相关文献
NATURE文献大全abstract::Nuclear pore complexes (NPCs) fuse the inner and outer membranes of the nuclear envelope. They comprise hundreds of nucleoporins (Nups) that assemble into multiple subcomplexes and form large central channels for nucleocytoplasmic exchange1,2. How this architecture facilitates messenger RNA export, NPC biogenesis and ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2670-5
更新日期:2020-10-01 00:00:00
abstract::As countries in Europe gradually relaxed lockdown restrictions after the first wave, test-trace-isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels1,2. Reviewing their shortcomings can provide elements to consider in light of the second wave that is current...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-03095-6
更新日期:2020-12-21 00:00:00
abstract::A major effect of insulin is to increase glucose transport in muscle and fat. A family of genes encoding distinct mammalian glucose transporters has recently been elucidated. One of these, the insulin-regulatable glucose transporter (IRGT), is primarily expressed in muscle and fat, tissues that exhibit insulin-depende...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/346369a0
更新日期:1990-07-26 00:00:00
abstract::Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08068
更新日期:2009-06-11 00:00:00
abstract::The observation that a few species in ecological communities are exceptionally abundant, whereas most are rare, prompted the development of species abundance models. Nevertheless, despite the large literature on the commonness and rarity of species inspired by these pioneering studies, some widespread empirical patter...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01547
更新日期:2003-04-17 00:00:00
abstract::The reversal or displacement of the retinal image by prism spectacles leads to extreme disruption of visually guided behaviour, but after an extended period of visual transformation normal behaviour is gradually restored. It is unclear whether this adaptation involves a change in visual perception, the learning of new...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/380523a0
更新日期:1996-04-11 00:00:00
abstract::Mechanical milling is an effective technique for the preparation of fine metallic and ceramic powders and can also be used to drive a wide range of chemical reactions. Milling devices include planetary machines, attritors and vibrational mills; products include amorphous, nanocrystalline and quasicrystalline materials...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature00985
更新日期:2002-09-12 00:00:00
abstract::The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with L...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09005
更新日期:2010-06-10 00:00:00
abstract::Networks have become a key approach to understanding systems of interacting objects, unifying the study of diverse phenomena including biological organisms and human society. One crucial step when studying the structure and dynamics of networks is to identify communities: groups of related nodes that correspond to fun...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09182
更新日期:2010-08-05 00:00:00
abstract::Chameleons are arboral lizards that spot their prey visually and catch it by highly precise shots with their long sticky tongue. They scan their environment by large-amplitude independent saccadic eye movements; once an insect is detected, the head axis is aligned towards the target ('head tracking', both eyes come fo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/373692a0
更新日期:1995-02-23 00:00:00
abstract::Felsenstein's application of the bootstrap method to evolutionary trees is one of the most cited scientific papers of all time. The bootstrap method, which is based on resampling and replications, is used extensively to assess the robustness of phylogenetic inferences. However, increasing numbers of sequences are now ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0043-0
更新日期:2018-04-01 00:00:00
abstract::Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09879
更新日期:2011-04-14 00:00:00
abstract::Antiviral T cells are thought to regulate whether hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections result in viral control, asymptomatic persistence or severe disease, although the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlatio...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10624
更新日期:2011-11-20 00:00:00
abstract::An analysis of 15 protein structures indicates: First, the loss of accessible surface area by monomeric proteins on folding-proportional to hydrophobic energy-is a simple function of molecular weight; second, the proportion of polar groups forming intramolecular hydrogen bonds is constant; and third, protein interiors...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/254304a0
更新日期:1975-03-27 00:00:00
abstract::Five new double-mutant haemoglobins composed of betaS chains and alpha chains with different substitutions, which are located at the surface of the tetramer, have been prepared. Although all the hybrids are more soluble than deoxyhaemoglobin S, the individual differences between these molecules make it possible to eva...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/260219a0
更新日期:1976-03-18 00:00:00
abstract::The radiation of the mammals provides a 165-million-year test case for evolutionary theories of how species occupy and then fill ecological niches. It is widely assumed that species often diverge rapidly early in their evolution, and that this is followed by a longer, drawn-out period of slower evolutionary fine-tunin...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10516
更新日期:2011-10-19 00:00:00
abstract::The manner in which phase transformations occur in solids determines important structural and physical properties of many materials. The main problem in characterizing the kinetic processes that occur during phase transformations is the difficulty of observing directly, in real time, the growth of one phase at the exp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35014569
更新日期:2000-06-01 00:00:00
abstract::In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton. Although most dissolved iron in the marine environment is complexed with organic molecules, picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone and serve as an im...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25982
更新日期:2018-03-22 00:00:00
abstract::Although freeze-fracture electron microscopy is normally analysed with the presumption that particles represent proteins embedded within the membrane, particles which appeared to represent inverted lipid micelles within membranes have been reported. I have now confirmed the occurrence of particles in protein-free lipo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/287166a0
更新日期:1980-09-11 00:00:00
abstract::The visual recognition of three-dimensional (3-D) objects on the basis of their shape poses at least two difficult problems. First, there is the problem of variable illumination, which can be addressed by working with relatively stable features such as intensity edges rather than the raw intensity images. Second, ther...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/343263a0
更新日期:1990-01-18 00:00:00
abstract::The success of cisplatin in cancer chemotherapy derives from its ability to crosslink DNA and alter the structure. Most cisplatin-DNA adducts are intrastrand d(GpG) and d(ApG) crosslinks, which unwind and bend the duplex to facilitate the binding of proteins that contain one or more high-mobility group (HMG) domains. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/377649a0
更新日期:1995-10-19 00:00:00
abstract::Synapse assembly requires trans-synaptic signals between the pre- and postsynapse, but our understanding of the essential organizational molecules involved in this process remains incomplete. Teneurin proteins are conserved, epidermal growth factor (EGF)-repeat-containing transmembrane proteins with large extracellula...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10923
更新日期:2012-03-18 00:00:00
abstract::The bacterial CRISPR/Cas9 system allows sequence-specific gene editing in many organisms and holds promise as a tool to generate models of human diseases, for example, in human pluripotent stem cells. CRISPR/Cas9 introduces targeted double-stranded breaks (DSBs) with high efficiency, which are typically repaired by no...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature17664
更新日期:2016-05-05 00:00:00
abstract::It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypo...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature23282
更新日期:2017-08-03 00:00:00
abstract::Rho is the essential RNA helicase that sets the borders between transcription units and adjusts transcriptional yield to translational needs in bacteria. Although Rho was the first termination factor to be discovered, the actual mechanism by which it reaches and disrupts the elongation complex (EC) is unknown. Here we...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08669
更新日期:2010-01-14 00:00:00
abstract::The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Ka...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/34193
更新日期:1998-01-01 00:00:00
abstract::Plant respiration results in an annual flux of carbon dioxide (CO2) to the atmosphere that is six times as large as that due to the emissions from fossil fuel burning, so changes in either will impact future climate. As plant respiration responds positively to temperature, a warming world may result in additional resp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature17142
更新日期:2016-03-31 00:00:00
abstract::China is the world's most populous country and a major emitter of greenhouse gases. Consequently, much research has focused on China's influence on climate change but somewhat less has been written about the impact of climate change on China. China experienced explosive economic growth in recent decades, but with only...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09364
更新日期:2010-09-02 00:00:00
abstract::Deep chlorophyll maxima (DCMs) are widespread in large parts of the world's oceans. These deep layers of high chlorophyll concentration reflect a compromise of phytoplankton growth exposed to two opposing resource gradients: light supplied from above and nutrients supplied from below. It is often argued that DCMs are ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04245
更新日期:2006-01-19 00:00:00
abstract::There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined approxima...
journal_title:Nature
pub_type: 杂志文章,多中心研究
doi:10.1038/nature05911
更新日期:2007-06-07 00:00:00