Abstract:
:The rapid turnover of the mammalian intestinal epithelium is supported by stem cells located around the base of the crypt. In addition to the Lgr5 marker, intestinal stem cells have been associated with other markers that are expressed heterogeneously within the crypt base region. Previous quantitative clonal fate analyses have led to the proposal that homeostasis occurs as the consequence of neutral competition between dividing stem cells. However, the short-term behaviour of individual Lgr5(+) cells positioned at different locations within the crypt base compartment has not been resolved. Here we establish the short-term dynamics of intestinal stem cells using the novel approach of continuous intravital imaging of Lgr5- Confetti mice. We find that Lgr5(+) cells in the upper part of the niche (termed 'border cells') can be passively displaced into the transit-amplifying domain, after the division of proximate cells, implying that the determination of stem-cell fate can be uncoupled from division. Through quantitative analysis of individual clonal lineages, we show that stem cells at the crypt base, termed 'central cells', experience a survival advantage over border stem cells. However, through the transfer of stem cells between the border and central regions, all Lgr5(+) cells are endowed with long-term self-renewal potential. These findings establish a novel paradigm for stem-cell maintenance in which a dynamically heterogeneous cell population is able to function long term as a single stem-cell pool.
journal_name
Naturejournal_title
Natureauthors
Ritsma L,Ellenbroek SIJ,Zomer A,Snippert HJ,de Sauvage FJ,Simons BD,Clevers H,van Rheenen Jdoi
10.1038/nature12972subject
Has Abstractpub_date
2014-03-20 00:00:00pages
362-365issue
7492eissn
0028-0836issn
1476-4687journal_volume
507pub_type
杂志文章相关文献
NATURE文献大全abstract::In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males. In 129-Ter/Ter mice, some of the r...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03595
更新日期:2005-05-19 00:00:00
abstract::Many small proteins seem to fold by a simple process explicable by conventional chemical kinetics and transition-state theory. This assumes an instant equilibrium between reactants and a high-energy activated state. In reality, equilibration occurs on timescales dependent on the molecules involved, below which such an...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01609
更新日期:2003-05-08 00:00:00
abstract::Climate models with increased levels of carbon dioxide predict that global warming causes heating in the tropics, but investigations of ancient climates based on palaeodata have generally indicated cool tropical temperatures during supposed greenhouse episodes. For example, in the Late Cretaceous and Eocene epochs the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35097000
更新日期:2001-10-04 00:00:00
abstract::Many corals bleach as a result of increased seawater temperature, which causes them to lose their vital symbiotic algae (Symbiodinium spp.) - unless these symbioses are able to adapt to global warming, bleaching threatens coral reefs worldwide. Here I show that some corals have adapted to higher temperatures, at least...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/430742a
更新日期:2004-08-12 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07631-3
更新日期:2018-12-01 00:00:00
abstract::Human activities are causing Earth's sixth major extinction event-an accelerating decline of the world's stocks of biological diversity at rates 100 to 1,000 times pre-human levels. Historically, low-impact intrusion into species habitats arose from local demands for food, fuel and living space. However, in today's in...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11145
更新日期:2012-06-06 00:00:00
abstract::The outcomes of evolution are determined by a stochastic dynamical process that governs how mutations arise and spread through a population. However, it is difficult to observe these dynamics directly over long periods and across entire genomes. Here we analyse the dynamics of molecular evolution in twelve experimenta...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature24287
更新日期:2017-11-02 00:00:00
abstract::Noradrenaline releases prostaglandins in the kidney, and in rats these augment rather than reduce vasoconstriction produced by the amine. Homogenates of kidneys of New Zealand rats inbred for hypertension exhibit lower prostaglandin inactivation by 15-hydroxydehydrogenase than controls. At the same time, augmentation ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/260582a0
更新日期:1976-04-15 00:00:00
abstract::Graphene oxide membranes-partially oxidized, stacked sheets of graphene-can provide ultrathin, high-flux and energy-efficient membranes for precise ionic and molecular sieving in aqueous solution. These materials have shown potential in a variety of applications, including water desalination and purification, gas and ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature24044
更新日期:2017-10-19 00:00:00
abstract::Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from mill...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12593
更新日期:2013-10-03 00:00:00
abstract::The process of DNA recognition by the activated form of the restriction endonuclease from E. coli K involves three enzyme-DNA complexes which can be differentiated experimentally. These are: an initial complex formed at a nonspecific site; a recognition complex involving the host specificity site; and a cleavage compl...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/256556a0
更新日期:1975-08-14 00:00:00
abstract::Molecular processes that govern pathogenic features of erythrocyte invasion and cytoadherence in malaria are reliant on Plasmodium-specific Duffy-binding-like domains (DBLs). These cysteine-rich modules recognize diverse host cell-surface receptors during pathogenesis. DBLs of parasite erythrocyte-binding proteins med...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04443
更新日期:2006-02-09 00:00:00
abstract::For life to be sustained, mistakes in DNA repair must be tolerated when damage obscures the genetic information. In bacteria such as Escherichia coli, DNA damage elicits the well regulated 'SOS response'. For the extreme case of damage that cannot be repaired by conventional enzymes, there are proteins that allow the ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/380727a0
更新日期:1996-04-25 00:00:00
abstract::Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and ro...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature22077
更新日期:2017-05-18 00:00:00
abstract::Nuclear exclusion of the PTEN (phosphatase and tensin homologue deleted in chromosome 10) tumour suppressor has been associated with cancer progression. However, the mechanisms leading to this aberrant PTEN localization in human cancers are currently unknown. We have previously reported that ubiquitinylation of PTEN a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07290
更新日期:2008-10-09 00:00:00
abstract::The extensive literature on the origin of the ratites focuses mainly on three questions: are the ratites mono- or polyphyletic, did they evolve from flying ancestors, and are they primitive or advanced? Opinion tends to accept a common descent from flying ancestors for the large ratites (for a summary of ideas see ref...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/287084a0
更新日期:1980-09-04 00:00:00
abstract::Understanding the pathogenesis of neuropsychiatric disorders is a substantial challenge for neurobiologists. It has long been hoped that identifying alleles that confer increased risk of such disorders would provide clues for neurobiological investigation. But this quest has been stymied by a lack of validated biologi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07454
更新日期:2008-10-16 00:00:00
abstract::The GAL4 protein activates transcription of the genes required for galactose utilization in Saccharomyces cerevisiae. The protein, consisting of 881 amino acids, is dimeric when bound to one of the approximately twofold symmetrical DNA sites present in the galactose upstream activating sequence (UASG). Here we use two...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/356450a0
更新日期:1992-04-02 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/d41586-018-07209-z
更新日期:2018-11-01 00:00:00
abstract::Landscapes modified by glacial erosion show a distinct distribution of surface area with elevation (hypsometry). In particular, the height of these regions is influenced by climatic gradients controlling the altitude where glacial and periglacial processes are the most active, and as a result, surface area is focused ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11786
更新日期:2013-01-10 00:00:00
abstract::Neurotransmitter release is initiated by influx of Ca2+ through voltage-gated Ca2+ channels, within 200 microseconds of the action potential arriving at the synaptic terminal, as the Ca2+ concentration increases from 100 nM to > 200 microM. Exocytosis requires high Ca2+ concentration, with a threshold of 20-50 microM ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/379451a0
更新日期:1996-02-01 00:00:00
abstract::Recent studies have shown that developing nerve fibres grow directly to their targets and are guided by specific cues, but the nature of these cues and the mechanism of guidance remain unknown. The growth of sympathetic axons towards an artificial source of nerve growth factor (NGF) in vivo and of sensory neurites up ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/306786a0
更新日期:1983-12-22 00:00:00
abstract::Ionic currents from individual K+ channels in squid axon membrane have been recorded. At hyperpolarizing membrane voltages, unit events occur as widely spaced rectangular pulses with short interruptions. The frequency of occurrence of the units increases strongly when the membrane is depolarized. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/285140a0
更新日期:1980-05-15 00:00:00
abstract::An optimal search theory, the so-called Lévy-flight foraging hypothesis, predicts that predators should adopt search strategies known as Lévy flights where prey is sparse and distributed unpredictably, but that Brownian movement is sufficiently efficient for locating abundant prey. Empirical studies have generated con...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09116
更新日期:2010-06-24 00:00:00
abstract::We describe an integrated physical, genetic and cytogenetic map of human chromosome 16 comprising both a low-resolution megaYAC map and a high-resolution cosmid contig/miniYAC map, which provides nearly complete coverage of the euchromatic arms of the chromosome. The physical map is anchored to a high-resolution cytog...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/377335a0
更新日期:1995-09-28 00:00:00
abstract::The formation of disulphide bonds is essential to the structure and function of proteins. These bonds rapidly form either cotranslationally or immediately post-translationally in the lumen of the endoplasmic reticulum. Native disulphide pairing for such proteins has been achieved in vitro; however, the rates of reasse...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/317267a0
更新日期:1985-09-19 00:00:00
abstract::Cell and lipid membranes are able to bend, as manifested during membrane fusion and the formation of non-lamellar lyotropic mesophases in water. But there is an energy cost to bending of lipid layers, called the curvature elastic energy. Although the functional form of this energy is known, a complete quantitative kno...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/368224a0
更新日期:1994-03-17 00:00:00
abstract::Decision making in an uncertain environment poses a conflict between the opposing demands of gathering and exploiting information. In a classic illustration of this 'exploration-exploitation' dilemma, a gambler choosing between multiple slot machines balances the desire to select what seems, on the basis of accumulate...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04766
更新日期:2006-06-15 00:00:00
abstract::Diminishing fossil fuel reserves and growing concerns about global warming indicate that sustainable sources of energy are needed in the near future. For fuels to be useful in the transportation sector, they must have specific physical properties that allow for efficient distribution, storage and combustion; these pro...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05923
更新日期:2007-06-21 00:00:00
abstract::Transforming viral proteins such as E1A force cells through the restriction point of the cell cycle into S phase by forming complexes with two cellular proteins: the retinoblastoma protein (Rb), a transcriptional co-repressor, and CBP/p300, a transcriptional co-activator. These two proteins locally influence chromatin...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/24190
更新日期:1998-11-12 00:00:00