Abstract:
:Blood production is ensured by rare, self-renewing haematopoietic stem cells (HSCs). How HSCs accommodate the diverse cellular stresses associated with their life-long activity remains elusive. Here we identify autophagy as an essential mechanism protecting HSCs from metabolic stress. We show that mouse HSCs, in contrast to their short-lived myeloid progeny, robustly induce autophagy after ex vivo cytokine withdrawal and in vivo calorie restriction. We demonstrate that FOXO3A is critical to maintain a gene expression program that poises HSCs for rapid induction of autophagy upon starvation. Notably, we find that old HSCs retain an intact FOXO3A-driven pro-autophagy gene program, and that ongoing autophagy is needed to mitigate an energy crisis and allow their survival. Our results demonstrate that autophagy is essential for the life-long maintenance of the HSC compartment and for supporting an old, failing blood system.
journal_name
Naturejournal_title
Natureauthors
Warr MR,Binnewies M,Flach J,Reynaud D,Garg T,Malhotra R,Debnath J,Passegué Edoi
10.1038/nature11895subject
Has Abstractpub_date
2013-02-21 00:00:00pages
323-7issue
7437eissn
0028-0836issn
1476-4687pii
nature11895journal_volume
494pub_type
杂志文章相关文献
NATURE文献大全abstract::In the prehistoric green Sahara of Holocene North Africa-in contrast to the Neolithic of Europe and Eurasia-a reliance on cattle, sheep and goats emerged as a stable and widespread way of life, long before the first evidence for domesticated plants or settled village farming communities. The remarkable rock art found ...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature11186
更新日期:2012-06-20 00:00:00
abstract::The three-dimensional structure of the 66-amino acid cro repressor protein of bacteriophage lambda suggests how it binds to its operator DNA. We propose that a dimer of cro protein is bound to the B-form of DNA with the 2-fold axis of the dimer coincident with the 2-fold axis of DNA. A pair of 2-fold-related alpha-hel...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/290754a0
更新日期:1981-04-30 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07674-6
更新日期:2018-12-01 00:00:00
abstract::The retina in most mammals contains two types of macroglial cells--Müller cells, which span the entire thickness of the retina, and astrocytes, which are mainly confined to the nerve fibre layer. Whereas Müller cells are diffusely distributed in all vertebrate retinae, the presence and distribution of retinal astrocyt...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/332834a0
更新日期:1988-04-28 00:00:00
abstract::Long-term depletion of the stratospheric ozone layer contributes to an increase in terrestrial solar ultraviolet-B radiation. This has deleterious effects on living organisms, such as DNA damage. When exposed to elevated ultraviolet-B radiation (UV-B; 280-315 nm), plants display a wide variety of physiological and mor...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35017595
更新日期:2000-07-06 00:00:00
abstract::The difficulty of working with the intact brain in vivo has led to the increasing use of nerve cell cultures in neurobiology. However, dissociated cells cannot be unambiguously identified by morphological criteria before the third week in culture, for it is not until then that the basic morphology and size of neurones...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/281376a0
更新日期:1979-10-04 00:00:00
abstract::A basic requirement for quantum information processing systems is the ability to completely control the state of a single qubit. For qubits based on electron spin, a universal single-qubit gate is realized by a rotation of the spin by any angle about an arbitrary axis. Driven, coherent Rabi oscillations between two sp...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07530
更新日期:2008-11-13 00:00:00
abstract::Only three elements are ferromagnetic at room temperature: the transition metals iron, cobalt and nickel. The Stoner criterion explains why iron is ferromagnetic but manganese, for example, is not, even though both elements have an unfilled 3d shell and are adjacent in the periodic table: according to this criterion, ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14621
更新日期:2015-08-06 00:00:00
abstract::Copper, zinc superoxide dismutase (SOD) catalyses the very rapid two-step dismutation of the toxic superoxide radical (O-2) to molecular oxygen and hydrogen peroxide through the alternate reduction and oxidation of the active-site copper. We report here that after refitting and further refinement of the previous 2 A s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/306284a0
更新日期:1983-11-17 00:00:00
abstract::In Drosophila and mice, olfactory receptor neurons (ORNs) expressing the same receptors have convergent axonal projections to specific glomerular targets in the antennal lobe/olfactory bulb, creating an odour map in this first olfactory structure of the central nervous system. Projection neurons of the Drosophila ante...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35102574
更新日期:2001-11-08 00:00:00
abstract::Injury causes a systemic inflammatory response syndrome (SIRS) that is clinically much like sepsis. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors. Similarly, cellular injury can release endogenous 'damage'-associated molecular patterns (DAMPs...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08780
更新日期:2010-03-04 00:00:00
abstract::Maternal immune activation (MIA) contributes to behavioural abnormalities associated with neurodevelopmental disorders in both primate and rodent offspring. In humans, epidemiological studies suggest that exposure of fetuses to maternal inflammation increases the likelihood of developing autism spectrum disorder. In p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature23910
更新日期:2017-09-28 00:00:00
abstract::We have investigated age-related reactivation of the X chromosome by devising a model in which reactivation of a single gene in one cell among many can be identified. We have used mice with an X-autosomal translocation giving consistent non-random inactivation of the normal X (as judged by biochemical and cytogenetic ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/327725a0
更新日期:1987-06-25 00:00:00
abstract::The large degeneracy of states resulting from the geometrical frustration of competing interactions is an essential ingredient of important problems in fields as diverse as magnetism, protein folding and neural networks. As first explained by Pauling, geometrical frustration of proton positions is also responsible for...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35092516
更新日期:2001-09-06 00:00:00
abstract::The theory of electric polarization in crystals defines the dipole moment of an insulator in terms of a Berry phase (geometric phase) associated with its electronic ground state. This concept not only solves the long-standing puzzle of how to calculate dipole moments in crystals, but also explains topological band str...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25777
更新日期:2018-03-14 00:00:00
abstract::During endocytosis, clathrin and the clathrin adaptor protein AP-2, assisted by a variety of accessory factors, help to generate an invaginated bud at the cell membrane. One of these factors is Eps15, a clathrin-coat-associated protein that binds the alpha-adaptin subunit of AP-2. Here we investigate the function of E...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/29555
更新日期:1998-08-20 00:00:00
abstract::The genetic relationships of human populations have been studied by comparing gene frequency data for protein and blood-group loci of different populations. DNA analysis now promises to be more informative since not only do the DNA coding sequences have more variation than their corresponding proteins but, in addition...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/319491a0
更新日期:1986-02-06 00:00:00
abstract::The ice-rich surface of the jovian satellite Europa is sparsely cratered, suggesting that this moon might be geologically active today. Moreover, models of the satellite's interior indicate that tidal interactions with Jupiter might produce enough heat to maintain a subsurface liquid water layer. But the mechanisms of...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/34862
更新日期:1998-01-22 00:00:00
abstract::Antifreeze proteins provide fish with protection against the freezing effect of polar environments by binding to ice surfaces and inhibiting growth of ice crystals. We present the X-ray crystal structure at 1.5 A resolution of a lone alpha-helical antifreeze protein from winter flounder, which provides a detailed look...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/375427a0
更新日期:1995-06-01 00:00:00
abstract::The optimal water transport system in plants should maximize hydraulic conductance (which is proportional to photosynthesis) for a given investment in transport tissue. To investigate how this optimum may be achieved, we have performed computer simulations of the hydraulic conductance of a branched transport system. H...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01444
更新日期:2003-02-27 00:00:00
abstract::Most neurons of the mammalian central nervous system (CNS) lose the ability to regenerate severed axons in vivo after a certain point in development. At least part of this loss in regenerative potential is intrinsic to neurons. Although embryonic retinal ganglion cells (RGCs) can grow axons into tectum of any age, mos...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/385434a0
更新日期:1997-01-30 00:00:00
abstract::Pairwise recognition of splice sites as a result of a scanning mechanism is an attractive model to explain the coordination of vertebrate splicing. Such a mechanism would predict a polarity-of-site recognition in the scanned unit, but no evidence for a polarity gradient across introns has been found. We have suggested...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/360277a0
更新日期:1992-11-19 00:00:00
abstract::Although there are substantial differences between the magnetospheres of Jupiter and Saturn, it has been suggested that cryovolcanic activity at Enceladus could lead to electrodynamic coupling between Enceladus and Saturn like that which links Jupiter with Io, Europa and Ganymede. Powerful field-aligned electron beams...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09928
更新日期:2011-04-21 00:00:00
abstract::The formation of condensed (compacted) protein phases is associated with a wide range of human disorders, such as eye cataracts, amyotrophic lateral sclerosis, sickle cell anaemia and Alzheimer's disease. However, condensed protein phases have their uses: as crystals, they are harnessed by structural biologists to elu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25971
更新日期:2018-04-04 00:00:00
abstract::It is thought that neutron stars in low-mass binary systems can accrete matter and angular momentum from the companion star and be spun-up to millisecond rotational periods. During the accretion stage, the system is called a low-mass X-ray binary, and bright X-ray emission is observed. When the rate of mass transfer d...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12470
更新日期:2013-09-26 00:00:00
abstract::In 1975-79, joint expeditions from Yale University and the Geological Survey of Pakistan (YGSP) recovered fossil lorisids in the Siwalik Group of Pakistan from four localities, spanning a period before 10 Myr ago to about 7 Myr ago. In three of the localities, only isolated teeth or fragments were found, whereas the f...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/289585a0
更新日期:1981-02-12 00:00:00
abstract::Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins. These precursors have unique, clonally ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35006664
更新日期:2000-03-30 00:00:00
abstract::Gut microbes supply the human body with energy from dietary polysaccharides through carbohydrate active enzymes, or CAZymes, which are absent in the human genome. These enzymes target polysaccharides from terrestrial plants that dominated diet throughout human evolution. The array of CAZymes in gut microbes is highly ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08937
更新日期:2010-04-08 00:00:00
abstract::Recently, several groups have initiated studies on cytosolic proteins that bind to isolated secretory vesicle membranes in the presence of Ca2+ in order to identify proteins that may regulate exocytosis. Two major chromaffin granule binding proteins, of molecular weights 32,000 (32K) and 34,000 (34K), were reported to...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/308208a0
更新日期:1984-03-08 00:00:00
abstract::The expression of immunodeficiency in patients with specific purine enzyme defects indicates a crucial role of the purine salvage pathway in the acquisition and expression of normal immune function. One current hypothesis links the failure of normal lymphocyte development in these diseases to the accumulation of deoxy...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/285494a0
更新日期:1980-06-12 00:00:00