Abstract:
:Glandular epithelia, including the mammary and prostate glands, are composed of basal cells (BCs) and luminal cells (LCs)1,2. Many glandular epithelia develop from multipotent basal stem cells (BSCs) that are replaced in adult life by distinct pools of unipotent stem cells1,3-8. However, adult unipotent BSCs can reactivate multipotency under regenerative conditions and upon oncogene expression3,9-13. This suggests that an active mechanism restricts BSC multipotency under normal physiological conditions, although the nature of this mechanism is unknown. Here we show that the ablation of LCs reactivates the multipotency of BSCs from multiple epithelia both in vivo in mice and in vitro in organoids. Bulk and single-cell RNA sequencing revealed that, after LC ablation, BSCs activate a hybrid basal and luminal cell differentiation program before giving rise to LCs-reminiscent of the genetic program that regulates multipotency during embryonic development7. By predicting ligand-receptor pairs from single-cell data14, we find that TNF-which is secreted by LCs-restricts BC multipotency under normal physiological conditions. By contrast, the Notch, Wnt and EGFR pathways were activated in BSCs and their progeny after LC ablation; blocking these pathways, or stimulating the TNF pathway, inhibited regeneration-induced BC multipotency. Our study demonstrates that heterotypic communication between LCs and BCs is essential to maintain lineage fidelity in glandular epithelial stem cells.
journal_name
Naturejournal_title
Natureauthors
Centonze A,Lin S,Tika E,Sifrim A,Fioramonti M,Malfait M,Song Y,Wuidart A,Van Herck J,Dannau A,Bouvencourt G,Dubois C,Dedoncker N,Sahay A,de Maertelaer V,Siebel CW,Van Keymeulen A,Voet T,Blanpain Cdoi
10.1038/s41586-020-2632-ysubject
Has Abstractpub_date
2020-08-01 00:00:00pages
608-613issue
7822eissn
0028-0836issn
1476-4687pii
10.1038/s41586-020-2632-yjournal_volume
584pub_type
杂志文章相关文献
NATURE文献大全abstract::The cyanobacterium Prochlorococcus is the dominant oxygenic phototroph in the tropical and subtropical regions of the world's oceans. It can grow at a range of depths over which light intensities can vary by up to 4 orders of magnitude. This broad depth distribution has been hypothesized to stem from the coexistence o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/30965
更新日期:1998-06-04 00:00:00
abstract::Neuropeptide Y (NPY) has a number of functions in mammalian physiology. Here we identify a role for NPY in promoting proliferation of postnatal neuronal precursor cells. NPY is synthesized in the postnatal olfactory epithelium by sustentacular cells, previously proposed to function only in structural support. Mice wit...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35073601
更新日期:2001-04-19 00:00:00
abstract::The silicate Earth is strongly depleted in moderately volatile elements (such as lead, zinc, indium and alkali elements) relative to CI chondrites, the meteorites that compositionally most closely resemble the Sun. This depletion may be explained qualitatively by accretion of 10 to 20 per cent of a volatile-rich body ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature23645
更新日期:2017-09-27 00:00:00
abstract::Since 1814, when rubella was first described, the origins of the disease and its causative agent, rubella virus (Matonaviridae: Rubivirus), have remained unclear1. Here we describe ruhugu virus and rustrela virus in Africa and Europe, respectively, which are, to our knowledge, the first known relatives of rubella viru...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2812-9
更新日期:2020-10-01 00:00:00
abstract::Since the discovery that epidermal growth factor (EGF) can accelerate opening of the eyelids, the EGF receptor (EGF-R) has been extensively studied and is now considered to be a prototype tyrosine kinase receptor. Binding of EGF or of transforming growth factor-alpha (TGF-alpha) or other related factors activates the ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/376337a0
更新日期:1995-07-27 00:00:00
abstract::Modification of tyrosine residues of proteins has attracted great interest. Although phosphorylation has received most attention, tyrosine-O-sulphation is also common and has been closely investigated in the hormones gastrin and cholecystokinin (CCK). CCK regulates pancreatic enzyme secretion. It is always sulphated a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/309456a0
更新日期:1984-05-31 00:00:00
abstract::Ecdysone in Drosophila has been a paradigm for steroid hormones since its ability to induce gene activity directly was demonstrated by its effects on moulting and polytene chromosome puffing. The ecdysone receptor (EcR) was recently confirmed as a member of the nuclear receptor superfamily by cloning and characterizat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/362471a0
更新日期:1993-04-01 00:00:00
abstract::Immunization of male and female animals with extracts of whole sperm cells is known to cause infertility. Also, men and women who spontaneously produce antisperm antibodies are infertile but otherwise healthy. Although the critical sperm antigens are unknown, these observations have led to the proposal that sperm prot...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/335543a0
更新日期:1988-10-06 00:00:00
abstract::The engrailed gene product of Drosophila specifies the fate of a subset of cells in each segment. Our studies of engrailed regulation suggest that fate determination is an elaborate, multistep process. At the time in embryogenesis when the engrailed-dependent cell fate is probably determined, four modes of control act...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/352404a0
更新日期:1991-08-01 00:00:00
abstract::In this Letter, the top structure of the right panel of Fig. 1a should be that of cis-9-octadecenoic acid, not trans-9-octadecenoic acid. Please see the accompanying Author Correction. This error has not been corrected online. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-019-0930-z
更新日期:2019-03-01 00:00:00
abstract::Interactions between animal viruses and antiviral antisera may exceptionally result in an apparent increase in viral infectivity. Halstead and coworkers demonstrated enhanced replication of dengue virus (a Flavivirus, family Togaviridae) in human or simian peripheral blood leucocytes carrying Fc receptors at subneutra...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/282509a0
更新日期:1979-11-29 00:00:00
abstract::It has been suggested that the initiation step in mouse skin carcinogenesis involves an alteration in epidermal-differentiation, as mouse basal keratinocytes exposed to initiators resist the arrest of cell growth that is normally associated with the induction of terminal differentiation by calcium ions. The growth of ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/314459a0
更新日期:1985-04-04 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07324-x
更新日期:2018-11-01 00:00:00
abstract::The human transcription factor Sp1 binds upstream of certain viral and cellular promoters and activates initiation of RNA synthesis from these promoters by RNA polymerase II. The Sp1 binding sites of both simian virus 40 and a related monkey promoter contain multiple copies of the sequence GGGCGG, three or four of the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/312409a0
更新日期:1984-11-29 00:00:00
abstract::The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase, but resistance arises rapidly, most frequently owing to the secondary T790M mutation withi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature17960
更新日期:2016-06-02 00:00:00
abstract::The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16INK4a tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/26155
更新日期:1998-09-17 00:00:00
abstract::The wavelength of light represents a fundamental technological barrier to the production of increasingly smaller features on integrated circuits. New technologies that allow the replication of patterns on scales less than 100 nm need to be developed if increases in computing power are to continue at the present rate. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35002540
更新日期:2000-02-24 00:00:00
abstract::In vertebrates the developing hindbrain is organized in segmental units. These units provide the primary grid for differentiation and axonal outgrowth. In the more anterior regions of the brain, however, the subdivisions remain more controversial. Cellular and molecular studies of the embryonic brain in lower vertebra...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/353267a0
更新日期:1991-09-19 00:00:00
abstract::The alpha beta T-cell receptors (TCRs) react with complex ligands composed of peptides bound to major histocompatibility complex (MHC) proteins. In the absence of foreign antigens the peptides bound to MHC molecules come from the proteins of the host itself. Interactions between TCRs and these self-peptide-MHC ligands...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/369151a0
更新日期:1994-05-12 00:00:00
abstract::Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12935
更新日期:2014-03-06 00:00:00
abstract::The classical theory of solids, based on the quantum mechanics of single electrons moving in periodic potentials, provides an excellent description of substances ranging from semiconducting silicon to superconducting aluminium. Over the last fifteen years, it has become increasingly clear that there are substances for...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01044
更新日期:2002-10-03 00:00:00
abstract::The fossil record of the living great apes is poor. New fossils from undocumented areas, particularly the equatorial forested habitats of extant hominoids, are therefore crucial for understanding their origins and evolution. Two main competing hypotheses have been proposed for orang-utan origins: dental similarities s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02245
更新日期:2004-01-29 00:00:00
abstract::Demethylation at distinct lysine residues in histone H3 by lysine-specific demethylase 1 (LSD1) causes either gene repression or activation. As a component of co-repressor complexes, LSD1 contributes to target gene repression by removing mono- and dimethyl marks from lysine 4 of histone H3 (H3K4). In contrast, during ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08839
更新日期:2010-04-01 00:00:00
abstract::In the era of precision cosmology, it is essential to determine the Hubble constant empirically with an accuracy of one per cent or better1. At present, the uncertainty on this constant is dominated by the uncertainty in the calibration of the Cepheid period-luminosity relationship2,3 (also known as the Leavitt law). ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-0999-4
更新日期:2019-03-01 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::During development, sympathetic neurons extend axons along a myriad of distinct trajectories, often consisting of arteries, to innervate one of a large variety of distinct final target tissues. Whether or not subsets of neurons within complex sympathetic ganglia are predetermined to innervate select end-organs is unkn...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06859
更新日期:2008-04-10 00:00:00
abstract::An amino acid sequence analysis of the N-terminal immunoglobulin heavy and light chain variable regions (VH and VL) from 16 hybridoma proteins which bind phosphorylcholine as well as the complete sequence analysis of 9 of these VH regions is presented. There seem to be more VH regions participating in the phosphorylch...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/291029a0
更新日期:1981-05-07 00:00:00
abstract::Quantum cryptography exploits the fundamental laws of quantum mechanics to provide a secure way to exchange private information. Such an exchange requires a common random bit sequence, called a key, to be shared secretly between the sender and the receiver. The basic idea behind quantum key distribution (QKD) has wide...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13303
更新日期:2014-05-22 00:00:00
abstract::Oxygenic photosynthesis in plants, algae and cyanobacteria is initiated at photosystem II, a homodimeric multisubunit protein-cofactor complex embedded in the thylakoid membrane. Photosystem II captures sunlight and powers the unique photo-induced oxidation of water to atmospheric oxygen. Crystallographic investigatio...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04224
更新日期:2005-12-15 00:00:00
abstract::The multi-disciplinary role of intermediate energy proton accelerators in pure and applied nuclear physics is discussed with particular reference to the experimental programmes at LAMPF (Los Alamos Meson Physics Facility) and SIN (Swiss Institute for Nuclear Research, Zurich). ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/270667a0
更新日期:1977-12-22 00:00:00