Abstract：
:Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Flores A,Schell J,Krall AS,Jelinek D,Miranda M,Grigorian M,Braas D,White AC,Zhou JL,Graham NA,Graeber T,Seth P,Evseenko D,Coller HA,Rutter J,Christofk HR,Lowry WEdoi
10.1038/ncb3575subject
Has Abstractpub_date
2017-09-01 00:00:00pages
1017-1026issue
9eissn
1465-7392issn
1476-4679pii
ncb3575journal_volume
19pub_type
杂志文章abstract：:Most invasive solid tumours display predominantly collective invasion, in which groups of cells invade the peritumoral stroma while maintaining cell-cell contacts. As the concepts and experimental models for functional analysis of collective cancer cell invasion are rapidly developing, we propose a framework for addre...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb2548
更新日期：2012-08-01 00:00:00
abstract：:TP53 (tumour protein 53) is one of the most frequently mutated genes in human cancer and its role during cellular transformation has been studied extensively. However, the homeostatic functions of p53 are less well understood. Here, we explore the molecular dependency network of TP53 through an RNAi-mediated synthetic...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2264
更新日期：2011-06-05 00:00:00
abstract：:The actin cytoskeleton has been implicated in restricting diffusion of plasma membrane components. Here, simultaneous observations of quantum dot-labelled FcepsilonRI motion and GFP-tagged actin dynamics provide direct evidence that actin filament bundles define micron-sized domains that confine mobile receptors. Dyna...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1755
更新日期：2008-08-01 00:00:00
abstract：:Pumilio proteins PUM1 and PUM2 are shown to regulate microRNA-dependent gene silencing by induction of a conformational switch in the 3' untranslated region of p27 mRNA. This conformational change is required for efficient microRNA-mediated repression of this cell-cycle regulator in rapidly proliferating cells. ...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb1010-928
更新日期：2010-10-01 00:00:00
abstract：:Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel expressed in a wide variety of epithelial cells, mutations of which are responsible for the hallmark defective chloride secretion observed in cystic fibrosis (CF). Although CFTR has been implicated in bicarbonate secretion,...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1047
更新日期：2003-10-01 00:00:00
abstract：:Parallel quantification of large numbers of messenger RNA transcripts using microarray technology promises to provide detailed insight into cellular processes involved in the regulation of gene expression. This should allow new understanding of signalling networks that operate in the cell and of the molecular basis an...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/35087138
更新日期：2001-08-01 00:00:00
abstract：:Dynamic regulation of adhesion complexes is required for cell migration and has therefore emerged as a key issue in the study of cell motility. Recent progress has been made in defining some of the molecular mechanisms by which adhesion disassembly is regulated, including the contributions of adhesion adaptor proteins...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1175
更新日期：2004-10-01 00:00:00
abstract：:The importance of herpes simplex viruses (HSV) as human pathogens and the emerging prospect of using mutant derivatives of HSV-1 as potential anti-cancer therapeutics have necessitated a thorough investigation into the molecular basis of host-cell permissiveness to HSV. Here we show that NIH-3T3 cells transformed with...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35087061
更新日期：2001-08-01 00:00:00
abstract：:Phosphoinositide 3-kinase (PI(3)K) is a unique enzyme characterized by both lipid and protein kinase activities. Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phospho...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1278
更新日期：2005-08-01 00:00:00
abstract：:The precise regulation of growth factor signalling is crucial to the molecular control of development in Drosophila. Post-translational modification of signalling molecules is one of the mechanisms that modulate developmental signalling specificity. We describe a new gene, fringe connection (frc), that encodes a nucle...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb0901-809
更新日期：2001-09-01 00:00:00
abstract：:Cells of multicellular organisms need to adopt specific morphologies. However, the molecular mechanisms bringing about membrane topology changes are far from understood-mainly because knowledge of membrane-shaping proteins that can promote local membrane curvatures is still limited. Our analyses unveiled that several ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0381-7
更新日期：2019-10-01 00:00:00
abstract：:Starvation of animals or cells triggers autophagic degradation of cell contents to retrieve nutrients, but, paradoxically, mitochondria enlarge. This is now shown to result from inhibition of mitochondrial fission through PKA-mediated phosphorylation of the GTPase DRP1. Elongation of mitochondria optimizes ATP product...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb0511-521
更新日期：2011-05-01 00:00:00
abstract：:Mammalian telomeres consist of non-coding TTAGGG repeats that are bound by the multi-protein complex 'shelterin', thus protecting chromosome ends from DNA repair mechanisms and degradation. Mammalian telomeric chromatin is enriched for the constitutive heterochromatin marks H3K9me3, H4K20me3 and HP1 (refs 2, 3, 4, 5, ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1685
更新日期：2008-02-01 00:00:00
abstract：:The directional movement of cells in a gradient of external stimulus is termed chemotaxis and is important in many aspects of development and differentiated cell function. Phophoinositide 3-kinases (PI(3)Ks) are thought to have critical roles within the gradient-sensing machinery of a variety of highly motile cells, s...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1517
更新日期：2007-01-01 00:00:00
abstract：:Metaphase spindles are microtubule-based structures that use a multitude of proteins to modulate their morphology and function. Today, we understand many details of microtubule assembly, the role of microtubule-associated proteins, and the action of molecular motors. Ultimately, the challenge remains to understand how...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2834
更新日期：2013-09-01 00:00:00
abstract：:The Ndc80 complex (Ndc80, Nuf2, Spc24 and Spc25) is a highly conserved kinetochore protein essential for end-on anchorage to spindle microtubule plus ends and for force generation coupled to plus-end polymerization and depolymerization. Spc24/Spc25 at one end of the Ndc80 complex binds the kinetochore. The N-terminal ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3323
更新日期：2016-04-01 00:00:00
abstract：:The cell division axis determines the future positions of daughter cells and is therefore critical for cell fate. The positioning of the division axis has been mostly studied in systems such as embryos or yeasts, in which cell shape is well defined. In these cases, cell shape anisotropy and cell polarity affect spindl...
journal_title：Nature cell biology
pub_type： 信件
doi：10.1038/ncb1307
更新日期：2005-10-01 00:00:00
abstract：:Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. However, the molecular details of micronucleus-based chromothripsis are still unclear. Now, an elegant system that specifically induces missegregation of the Y chromosome provides insight into this process,...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3458
更新日期：2016-12-23 00:00:00
abstract：:The double fertilization process in angiosperms is based on the delivery of a pair of sperm cells by the pollen tube (the male gametophyte), which elongates towards an embryo sac (the female gametophyte) enclosing an egg and a central cell. Several studies have described the mechanisms of gametophyte interaction, and ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1345
更新日期：2006-01-01 00:00:00
abstract：:A surprising functional association between TRPM3, a mysterious member of the family of transient receptor potential (TRP) cation channels, and the sulphated version of pregnenolone, 'mother' of all steroid hormones, has been identified. ...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb1208-1383
更新日期：2008-12-01 00:00:00
abstract：:Animal cell cytokinesis results from patterned activation of the small GTPase Rho, which directs assembly of actomyosin in the equatorial cortex. Cytokinesis is restricted to a portion of the cell cycle following anaphase onset in which the cortex is responsive to signals from the spindle. We show that shortly after a...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3251
更新日期：2015-11-01 00:00:00
abstract：:Proteins essential for vesicle formation by the Coat Protein I (COPI) complex are being identified, but less is known about the role of specific lipids. Brefeldin-A ADP-ribosylated substrate (BARS) functions in the fission step of COPI vesicle formation. Here, we show that BARS induces membrane curvature in cooperatio...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1774
更新日期：2008-10-01 00:00:00
abstract：:The presence of disseminated tumour cells (DTCs) in bone marrow is predictive of poor metastasis-free survival of patients with breast cancer with localized disease. DTCs persist in distant tissues despite systemic administration of adjuvant chemotherapy. Many assume that this is because the majority of DTCs are quies...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-018-0267-0
更新日期：2019-02-01 00:00:00
abstract：:Coordination of microtubules and the actin cytoskeleton is important in several types of cell movement. mDia1 is a member of the formin-homology family of proteins and an effector of the small GTPase Rho. It contains the Rho-binding domain in its amino terminus and two distinct regions of formin homology, FH1 in the m...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35050598
更新日期：2001-01-01 00:00:00
abstract：:Autophagy is an evolutionarily conserved 'self-eating' process. Although the genes essential for autophagy (named Atg) have been identified in yeast, the molecular mechanism of how Atg proteins control autophagosome formation in mammalian cells remains to be elucidated. Here, we demonstrate that Bif-1 (also known as E...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1634
更新日期：2007-10-01 00:00:00
abstract：:Protein degradation in eukaryotes often requires the ubiquitin-selective chaperone p97 for substrate recruitment and ubiquitin-chain assembly. However, the physiological relevance of p97, and its role in developmental processes, remain unclear. Here, we discover an unanticipated function for CDC-48/p97 in myosin assem...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1554
更新日期：2007-04-01 00:00:00
abstract：:mTOR (mammalian target of rapamycin) signalling and macroautophagy (henceforth autophagy) regulate numerous pathological and physiological processes, including cellular responses to altered nutrient levels. However, the mechanisms regulating mTOR and autophagy remain incompletely understood. Lysosomes are dynamic intr...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2204
更新日期：2011-04-01 00:00:00
abstract：:Here we show that segregation of homologous chromosomes and that of sister chromatids are differentially regulated in Xenopus and possibly in other higher eukaryotes. Upon hormonal stimulation, Xenopus oocytes microinjected with antibodies against the anaphase-promoting complex (APC) activator Fizzy or the APC core su...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35050607
更新日期：2001-01-01 00:00:00
abstract：:Cancer-induced immune responses affect tumour progression and therapeutic response. In multiple murine models and clinical datasets, we identified large variations of neutrophils and macrophages that define 'immune subtypes' of triple-negative breast cancer (TNBC), including neutrophil-enriched (NES) and macrophage-en...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0373-7
更新日期：2019-09-01 00:00:00
abstract：:Brown adipose tissue is a key metabolic organ that oxidizes fatty acids and glucose to generate heat. Through epigenomic analyses of multiple adipose depots, the transcription factor nuclear factor I-A (NFIA) is now shown to drive the brown fat genetic program through binding to lineage-specific cis-regulatory element...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3591
更新日期：2017-08-31 00:00:00
