Abstract:
:Epithelial organs undergo steady-state turnover throughout adult life, with old cells being continually replaced by the progeny of stem cell divisions. To avoid hyperplasia or atrophy, organ turnover demands strict equilibration of cell production and loss. However, the mechanistic basis of this equilibrium is unknown. Here we show that robustly precise turnover of the adult Drosophila intestine arises through a coupling mechanism in which enterocyte apoptosis breaks feedback inhibition of stem cell division. Healthy enterocytes inhibit stem cell division through E-cadherin, which prevents secretion of mitogenic epidermal growth factors (EGFs) by repressing transcription of the EGF maturation factor rhomboid. Individual apoptotic enterocytes promote divisions by loss of E-cadherin, which releases cadherin-associated β-catenin (Armadillo in Drosophila) and p120-catenin to induce rhomboid. Induction of rhomboid in the dying enterocyte triggers activation of the EGF receptor (Egfr) in stem cells within a discrete radius. When we blocked apoptosis, E-cadherin-controlled feedback suppressed divisions, and the organ retained the same number of cells. When we disrupted feedback, apoptosis and divisions were uncoupled, and the organ developed either hyperplasia or atrophy. Together, our results show that robust cellular balance hinges on the obligate coupling of divisions to apoptosis, which limits the proliferative potential of a stem cell to the precise time and place at which a replacement cell is needed. In this way, localized cell-cell communication gives rise to tissue-level homeostatic equilibrium and constant organ size.
journal_name
Naturejournal_title
Natureauthors
Liang J,Balachandra S,Ngo S,O'Brien LEdoi
10.1038/nature23678subject
Has Abstractpub_date
2017-08-31 00:00:00pages
588-591issue
7669eissn
0028-0836issn
1476-4687pii
nature23678journal_volume
548pub_type
杂志文章相关文献
NATURE文献大全abstract::In order to direct a movement towards a visual stimulus, visual spatial information must be combined with postural information. For example, directing gaze (eye plus head) towards a visible target requires the combination of retinal image location with eye and head position to determine the location of the target rela...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/29777
更新日期:1998-08-27 00:00:00
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 pr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11463
更新日期:2012-11-29 00:00:00
abstract::Homologous recombination is a molecular process that has multiple important roles in DNA metabolism, both for DNA repair and genetic variation in all forms of life. Generally, homologous recombination involves the exchange of genetic information between two identical or nearly identical DNA molecules; however, homolog...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13682
更新日期:2014-11-20 00:00:00
abstract::Humans differ from other primates in their significantly lengthened growth period. The persistence of a fetal pattern of brain growth after birth is another important feature of human development. Here we present the results of an analysis of the 1.8-million-year-old Mojokerto child (Perning 1, Java), the only well pr...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature02852
更新日期:2004-09-16 00:00:00
abstract::Regulation of the rapid compensatory growth seen in the remaining adrenal gland of rats following unilateral adrenalectomy is poorly understood. The role of adrenocorticotropic hormone (ACTH) is obscure as immunoneutralization of circulating ACTH does not affect the observed compensatory growth or hyperplasia. This fi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/306070a0
更新日期:1983-11-03 00:00:00
abstract::A long-standing goal of artificial intelligence is an algorithm that learns, tabula rasa, superhuman proficiency in challenging domains. Recently, AlphaGo became the first program to defeat a world champion in the game of Go. The tree search in AlphaGo evaluated positions and selected moves using deep neural networks....
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature24270
更新日期:2017-10-18 00:00:00
abstract::Reinforcement learning models postulate that neurons that release dopamine encode information about action and action outcome, and provide a teaching signal to striatal spiny projection neurons in the form of dopamine release1. Dopamine is thought to guide learning via dynamic and differential modulation of protein ki...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-03050-5
更新日期:2020-12-23 00:00:00
abstract::Electron transfer reactions are essential for life because they underpin oxidative phosphorylation and photosynthesis, processes leading to the generation of ATP, and are involved in many reactions of intermediary metabolism. Key to these roles is the formation of transient inter-protein electron transfer complexes. T...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11996
更新日期:2013-04-04 00:00:00
abstract::Recent studies have shown that short chemically synthesized peptides very often induce antibodies which react with the cognate sequence in the intact folded protein. Since such antibodies react with known regions of proteins, they are of predetermined specificity and offer a precision not previously possible with immu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/306697a0
更新日期:1983-12-15 00:00:00
abstract::The origins of the building blocks of the Solar System can be studied using the isotopic composition of early planetary and meteoritic material. Oxygen isotopes in planetary materials show variations at the per cent level that are not related to the mass of the isotopes; rather, they result from the mixture of compone...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03947
更新日期:2005-09-15 00:00:00
abstract::Milankovitch proposed that summer insolation at mid-latitudes in the Northern Hemisphere directly causes the ice-age climate cycles. This would imply that times of ice-sheet collapse should correspond to peaks in Northern Hemisphere June insolation. But the penultimate deglaciation has proved controversial because Jun...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35003541
更新日期:2000-03-02 00:00:00
abstract::The yeast nuclear protein Yra1p is an essential export factor for mRNA. Yra1p interacts directly with the mRNA transport factor Mex67p/Mtr2p, which is associated with the nuclear pore. Here, we report a genetic interaction between YRA1 and SUB2, the gene for a DEAD box helicase involved in splicing. Mutation of SUB2 a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35098113
更新日期:2001-10-11 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,信件
doi:10.1038/d41586-019-00764-z
更新日期:2019-03-01 00:00:00
abstract::The retinotectal projection has long been studied experimentally and theoretically, as a model for the formation of topographic brain maps. Neighbouring retinal ganglion cells (RGCs) project their axons to neighbouring positions in the optic tectum, thus re-establishing a continuous neural representation of visual spa...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06816
更新日期:2008-04-17 00:00:00
abstract::Parkinson's disease is the second most common neurodegenerative disorder. Growing evidence indicates a causative role of misfolded forms of the protein α-synuclein in the pathogenesis of Parkinson's disease. Intraneuronal aggregates of α-synuclein occur in Lewy bodies and Lewy neurites, the cytopathological hallmarks ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10324
更新日期:2011-08-14 00:00:00
abstract::Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10-15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (brea...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature20099
更新日期:2016-11-03 00:00:00
abstract::The giant polytene chromosomes of Drosophila melanogaster have long been of interest to the geneticist because of the visible map of the genome provided by their characteristic banding patterns. An issue in the understanding of the molecular basis of chromosome banding has been whether the chromosomal DNA is replicate...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/307176a0
更新日期:1984-01-12 00:00:00
abstract::Class-V myosin proceeds along actin filaments with large ( approximately 36 nm) steps. Myosin-V has two heads, each of which consists of a motor domain and a long (23 nm) neck domain. In accordance with the widely accepted lever-arm model, it was suggested that myosin-V steps to successive (36 nm) target zones along t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/415192a
更新日期:2002-01-10 00:00:00
abstract::Mammal-like reptiles of the order Therapsida document the emergence of mammals from more primitive synapsids and are of unique zoological and palaeontological interest on that account. Therapsids, first appearing in the Early Permian, were thought to become extinct in the Middle Jurassic, soon after the Late Triassic ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/358233a0
更新日期:1992-07-16 00:00:00
abstract::S-100 protein, one of the unique proteins found in the nervous system, has recently been discovered unexpectedly in the rat anterior pituitary. Immunocytochemistry reveals that stellate, follicular and folliculostellate cells, and marginal cells of the rat anterior pituitary contain this protein; however, as far as we...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/303711a0
更新日期:1983-06-23 00:00:00
abstract::Organic photovoltaic cells are now approaching commercially viable efficiencies, particularly for applications that make use of their unique potential for flexibility and semitransparency1-3. However, their reliability remains a major concern, as even the most stable devices reported so far degrade within only a few y...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1544-1
更新日期:2019-09-01 00:00:00
abstract::The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature18637
更新日期:2016-07-21 00:00:00
abstract::It has been proposed that the trans-sarcolemmal influx of Ca2+ occurring during the plateau of the mammalian cardiac action potentials is insufficient in itself to activate the myofilaments, but can trigger a release of Ca2+ from the sarcoplasmic reticulum (SR) which is sufficient for activation. The demonstration of ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/281146a0
更新日期:1979-09-13 00:00:00
abstract::Change history: In this Letter, the received date should be 20 December 2017, instead of 27 April 2018. This has been corrected online. ...
journal_title:Nature
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41586-018-0314-9
更新日期:2018-10-01 00:00:00
abstract::Protoplanetary disks are known to possess a variety of substructures in the distribution of their millimetre-sized grains, predominantly seen as rings and gaps1, which are frequently interpreted as arising from the shepherding of large grains by either hidden, still-forming planets within the disk2 or (magneto-)hydrod...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1642-0
更新日期:2019-10-01 00:00:00
abstract::Thomas et al. argue, contrary to Sala et al. that climate change poses an equal or greater threat to global biodiversity than land-use change. We contest this claim, however, on the grounds that Thomas et al. incorrectly apply species-area relationships. ...
journal_title:Nature
pub_type: 评论,杂志文章
doi:10.1038/nature02717
更新日期:2004-07-01 00:00:00
abstract::Many receptors for neuropeptides and hormones are coupled with the heterotrimeric G(i) protein, which activates the p42/44 mitogen-activated protein kinase (ERK/MAPK) cascade through both the alpha- and betagamma-subunits of G(i). The betagamma-subunit activates the ERK/MAPK cascade through tyrosine kinase. Constituti...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/23738
更新日期:1999-08-26 00:00:00
abstract::Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13903
更新日期:2015-01-29 00:00:00
abstract::Symbolic arithmetic is fundamental to science, technology and economics, but its acquisition by children typically requires years of effort, instruction and drill. When adults perform mental arithmetic, they activate nonsymbolic, approximate number representations, and their performance suffers if this nonsymbolic sys...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05850
更新日期:2007-05-31 00:00:00
abstract::Conjugate (or 1,4-) additions of carbanionic species to α,β-unsaturated carbonyl compounds are vital to research in organic and medicinal chemistry, and there are several chiral catalysts that facilitate the catalytic enantioselective additions of nucleophiles to enoates. Nonetheless, catalytic enantioselective 1,6-co...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature19063
更新日期:2016-09-15 00:00:00