Counting human somatic cell replications: methylation mirrors endometrial stem cell divisions.

Abstract:

:Cell proliferation may be altered in many diseases, but it is uncertain exactly how to measure total numbers of divisions. Although it is impossible to count every division directly, potentially total numbers of stem cell divisions since birth may be inferred from numbers of somatic errors. The idea is that divisions are surreptitiously recorded by random errors that occur during replication. To test this "molecular clock" hypothesis, epigenetic errors encoded in certain methylation patterns were counted in glands from 30 uteri. Endometrial divisions can differ among women because of differences in estrogen exposures or numbers of menstrual cycles. Consistent with an association between mitotic age and methylation, there was an age-related increase in methylation with stable levels after menopause, and significantly less methylation was observed in lean or older multiparous women. Methylation patterns were diverse and more consistent with niche rather than immortal stem cell lineages. There was no evidence for decreased stem cell survival with aging. An ability to count lifetime numbers of stem cell divisions covertly recorded by random replication errors provides new opportunities to link cell proliferation with aging and cancer.

authors

Kim JY,Tavaré S,Shibata D

doi

10.1073/pnas.0503976102

keywords:

subject

Has Abstract

pub_date

2005-12-06 00:00:00

pages

17739-44

issue

49

eissn

0027-8424

issn

1091-6490

pii

0503976102

journal_volume

102

pub_type

杂志文章
  • Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction.

    abstract::Extracellular matrix (ECM) profoundly influences the growth and differentiation of the mammary gland epithelium, both in culture and in vivo. Utilizing a clonal population of mouse mammary epithelial cells that absolutely requires an exogenous ECM for function, we developed a rapid assay to study signal transduction b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.26.12378

    authors: Roskelley CD,Desprez PY,Bissell MJ

    更新日期:1994-12-20 00:00:00

  • The rat suprachiasmatic nucleus is a clock for all seasons.

    abstract::Seasonal changes of daylength (photoperiod) affect the expression of hormonal and behavioral circadian rhythms in a variety of organisms. In mammals, such effects might reflect photoperiodic changes in the circadian pace-making system [located in the suprachiasmatic nucleus (SCN) of the hypothalamus] that governs thes...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.17.7754

    authors: Sumová A,Trávnícková Z,Peters R,Schwartz WJ,Illnerová H

    更新日期:1995-08-15 00:00:00

  • Monolayer purification: a rapid method for isolating protein complexes for single-particle electron microscopy.

    abstract::Visualizing macromolecular complexes by single-particle electron microscopy (EM) entails stringent biochemical purification, specimen preparation, low-dose imaging, and 3D image reconstruction. Here, we introduce the "monolayer purification" method, which employs nickel-nitrilotriacetic acid (Ni-NTA) functionalized li...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0800867105

    authors: Kelly DF,Dukovski D,Walz T

    更新日期:2008-03-25 00:00:00

  • Locations of adenovirus genes required for the replication of adenovirus-associated virus.

    abstract::We have used DNA transfection to identify several regions of the adenovirus genome needed to induce replication of the defective parvovirus, adenovirus-associated virus (AAV). Previous studies have indicated that only early adenovirus functions are needed to aid the replication of AAV. In this report, we demonstrate t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.3.1925

    authors: Janik JE,Huston MM,Rose JA

    更新日期:1981-03-01 00:00:00

  • Precise CRISPR/Cas9 editing of the NHE1 gene renders chickens resistant to the J subgroup of avian leukosis virus.

    abstract::Avian leukosis virus subgroup J (ALV-J) is an important concern for the poultry industry. Replication of ALV-J depends on a functional cellular receptor, the chicken Na+/H+ exchanger type 1 (chNHE1). Tryptophan residue number 38 of chNHE1 (W38) in the extracellular portion of this molecule is a critical amino acid for...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1913827117

    authors: Koslová A,Trefil P,Mucksová J,Reinišová M,Plachý J,Kalina J,Kučerová D,Geryk J,Krchlíková V,Lejčková B,Hejnar J

    更新日期:2020-01-28 00:00:00

  • Mitochondrial complex I inhibition is not required for dopaminergic neuron death induced by rotenone, MPP+, or paraquat.

    abstract::Inhibition of mitochondrial complex I is one of the leading hypotheses for dopaminergic neuron death associated with Parkinson's disease (PD). To test this hypothesis genetically, we used a mouse strain lacking functional Ndufs4, a gene encoding a subunit required for complete assembly and function of complex I. Delet...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0807581105

    authors: Choi WS,Kruse SE,Palmiter RD,Xia Z

    更新日期:2008-09-30 00:00:00

  • Systematic transcriptome analysis reveals tumor-specific isoforms for ovarian cancer diagnosis and therapy.

    abstract::Tumor-specific molecules are needed across diverse areas of oncology for use in early detection, diagnosis, prognosis and therapy. Large and growing public databases of transcriptome sequencing data (RNA-seq) derived from tumors and normal tissues hold the potential of yielding tumor-specific molecules, but because th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1508057112

    authors: Barrett CL,DeBoever C,Jepsen K,Saenz CC,Carson DA,Frazer KA

    更新日期:2015-06-09 00:00:00

  • Limits of multifunctionality in tunable networks.

    abstract::Nature is rife with networks that are functionally optimized to propagate inputs to perform specific tasks. Whether via genetic evolution or dynamic adaptation, many networks create functionality by locally tuning interactions between nodes. Here we explore this behavior in two contexts: strain propagation in mechanic...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1806790116

    authors: Rocks JW,Ronellenfitsch H,Liu AJ,Nagel SR,Katifori E

    更新日期:2019-02-12 00:00:00

  • Design and construction of diverse mammalian prion strains.

    abstract::Prions are infectious proteins that encipher biological information within their conformations; variations in these conformations dictate different prion strains. Toward elucidating the molecular language of prion protein (PrP) conformations, we produced an array of recombinant PrP amyloids with varying conformational...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910350106

    authors: Colby DW,Giles K,Legname G,Wille H,Baskakov IV,DeArmond SJ,Prusiner SB

    更新日期:2009-12-01 00:00:00

  • Structural basis for the interaction of Escherichia coli NusA with protein N of phage lambda.

    abstract::The C terminus of transcription factor NusA from Escherichia coli comprises two repeat units, which bind during antitermination to protein N from phage lambda. To delineate the structural basis of the NusA-lambdaN interaction, we attempted to crystallize the NusA C-terminal repeats in complex with a lambdaN peptide (r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0405883101

    authors: Bonin I,Mühlberger R,Bourenkov GP,Huber R,Bacher A,Richter G,Wahl MC

    更新日期:2004-09-21 00:00:00

  • Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors.

    abstract::The polyhedral borane ion [n-B20H18]2- reacts with liquid ammonia in the presence of a suitable base to produce an apical-equatorial (ae) isomer of the [B20H17NH3]3- ion, [1-(2'-B10H9)-2-NH3B10H8]3-. The structure of this product has been confirmed by 11B NMR spectroscopy and x-ray crystallography. This species underg...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.8.3029

    authors: Feakes DA,Shelly K,Knobler CB,Hawthorne MF

    更新日期:1994-04-12 00:00:00

  • Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex.

    abstract::Nuclear factor of activated T cells (NFAT) proteins are Ca(2+)-regulated transcription factors that control gene expression in many cell types. NFAT proteins are heavily phosphorylated and reside in the cytoplasm of resting cells; when cells are stimulated by a rise in intracellular Ca(2+), NFAT proteins are dephospho...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1019711108

    authors: Sharma S,Findlay GM,Bandukwala HS,Oberdoerffer S,Baust B,Li Z,Schmidt V,Hogan PG,Sacks DB,Rao A

    更新日期:2011-07-12 00:00:00

  • An unusual active hexose transport system in human and mouse preimplantation embryos.

    abstract::In a metabolic study of human and mouse preimplantation embryos (preembryos), we measured glucose uptake and phosphorylation with nonradioactive 2-deoxyglucose (DG) as tracer. Initial experiments indicated an active hexose transport capacity, a property thought to be restricted in mammals to intestinal villi and kidne...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.21.10023

    authors: Chi MM,Manchester JK,Basuray R,Mahendra S,Strickler RC,McDougal DB Jr,Lowry OH

    更新日期:1993-11-01 00:00:00

  • The number of D and E regions in the fibrinogen molecule.

    abstract::The regional structure of fibrinogen was considered in reference to the terminal plasmin-cleavage fragments, D and E. By two independent approaches, a yield of two D and two E fragments was determined and this established the presence of two D and two E regions in each fibrinogen molecule. Immunochemically, it was sho...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.1.158

    authors: Plow EF,Edgington TS

    更新日期:1974-01-01 00:00:00

  • Identification and genetic mapping of a homeobox gene to the 4p16.1 region of human chromosome 4.

    abstract::A human craniofacial cDNA library was screened with a degenerate oligonucleotide probe based on the conserved third helix of homeobox genes. From this screening, we identified a homeobox gene, H6, which shared only 57-65% amino acid identity to previously reported homeodomains. H6 was physically mapped to the 4p16.1 r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.23.11579

    authors: Stadler HS,Padanilam BJ,Buetow K,Murray JC,Solursh M

    更新日期:1992-12-01 00:00:00

  • Induction of glucose-regulated proteins during anaerobic exposure and of heat-shock proteins after reoxygenation.

    abstract::In this report we examine the effects of chronic anaerobic exposure and subsequent reoxygenation on protein synthesis patterns in Chinese hamster ovary cells. It is observed by two-dimensional gel electrophoresis (isoelectric focusing/NaDodSO4/PAGE) that the transition from an atmospheric environment to an anaerobic s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.15.4843

    authors: Sciandra JJ,Subjeck JR,Hughes CS

    更新日期:1984-08-01 00:00:00

  • Evolution of antifreeze glycoprotein gene from a trypsinogen gene in Antarctic notothenioid fish.

    abstract::Freezing avoidance conferred by different types of antifreeze proteins in various polar and subpolar fishes represents a remarkable example of cold adaptation, but how these unique proteins arose is unknown. We have found that the antifreeze glycoproteins (AFGPs) of the predominant Antarctic fish taxon, the notothenio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.8.3811

    authors: Chen L,DeVries AL,Cheng CH

    更新日期:1997-04-15 00:00:00

  • Location of the 18/28S ribosomal RNA genes in two Hawaiian Drosophila species by monoclonal immunological identification of RNA.DNA hybrids in situ.

    abstract::Using both heterologous rabbit antisera and mouse monoclonal antibody to RNA.DNA hybrids, we have mapped the in situ hybridization locus of the 18/28S ribosomal RNA fraction to a single large band on polytene autosome 3 in Drosophila heteroneura and Drosophila silvestris. This portion of the chromosome is not physical...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.6.3751

    authors: Stuart WD,Bishop JG,Carson HL,Frank MB

    更新日期:1981-06-01 00:00:00

  • Retinoid X receptor alpha forms tetramers in solution.

    abstract::Protein-protein interactions allow the retinoid X receptor (RXR) to bind to cognate DNA as a homo- or a heterodimer and to participate in mediating the effects of a variety of hormones on gene transcription. Here we report a systematic study of the oligomeric state of RXR in the absence of a DNA template. We have used...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.19.8645

    authors: Kersten S,Kelleher D,Chambon P,Gronemeyer H,Noy N

    更新日期:1995-09-12 00:00:00

  • Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands.

    abstract::Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adja...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.12890

    authors: Dickinson LA,Gulizia RJ,Trauger JW,Baird EE,Mosier DE,Gottesfeld JM,Dervan PB

    更新日期:1998-10-27 00:00:00

  • Heterogeneity of long-history migration explains cultural differences in reports of emotional expressivity and the functions of smiles.

    abstract::A small number of facial expressions may be universal in that they are produced by the same basic affective states and recognized as such throughout the world. However, other aspects of emotionally expressive behavior vary widely across culture. Just why do they vary? We propose that some cultural differences in expre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1413661112

    authors: Rychlowska M,Miyamoto Y,Matsumoto D,Hess U,Gilboa-Schechtman E,Kamble S,Muluk H,Masuda T,Niedenthal PM

    更新日期:2015-05-12 00:00:00

  • Starch grain and phytolith evidence for early ninth millennium B.P. maize from the Central Balsas River Valley, Mexico.

    abstract::Questions that still surround the origin and early dispersals of maize (Zea mays L.) result in large part from the absence of information on its early history from the Balsas River Valley of tropical southwestern Mexico, where its wild ancestor is native. We report starch grain and phytolith data from the Xihuatoxtla ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.0812525106

    authors: Piperno DR,Ranere AJ,Holst I,Iriarte J,Dickau R

    更新日期:2009-03-31 00:00:00

  • Competition for mates and the improvement of nonsexual fitness.

    abstract::Competition for mates can be a major source of selection, not just on secondary sexual traits but across the genome. Mate competition strengthens selection on males via sexual selection, which typically favors healthy, vigorous individuals and, thus, all genetic variants that increase overall quality. However, recent ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1805435115

    authors: Yun L,Chen PJ,Kwok KE,Angell CS,Rundle HD,Agrawal AF

    更新日期:2018-06-26 00:00:00

  • Adenosine receptors in brain membranes: binding of N6-cyclohexyl[3H]adenosine and 1,3-diethyl-8-[3H]phenylxanthine.

    abstract::N6-Cyclohexyl[3H]adenosine ([3H]CHA) and 1,3-diethyl-8-[3H]phenylxanthine ([3H]DPX) to bind to adenosine receptors in brain membranes. The agonist [3H]CHA has high affinity in both bovine and guinea pig brain (Kd, 0.7 nM and 6 nM, respectively). [3H]CHA binding kinetics are slow (dissociation t1/2;60 min); binding is ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.9.5547

    authors: Bruns RF,Daly JW,Snyder SH

    更新日期:1980-09-01 00:00:00

  • Algorithm for cellular reprogramming.

    abstract::The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predic...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1712350114

    authors: Ronquist S,Patterson G,Muir LA,Lindsly S,Chen H,Brown M,Wicha MS,Bloch A,Brockett R,Rajapakse I

    更新日期:2017-11-07 00:00:00

  • Assaying gene content in Arabidopsis.

    abstract::Arabidopsis has been popular as a model plant system for decades. Completion of the Arabidopsis genome and the availability of large expressed sequence-tag collections from other dicot species provides an opportunity to assess gene content in Arabidopsis, specifically by identifying genes from dicot test species that ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.142126599

    authors: Allen KD

    更新日期:2002-07-09 00:00:00

  • Nascent RNA sequencing reveals distinct features in plant transcription.

    abstract::Transcriptional regulation of gene expression is a major mechanism used by plants to confer phenotypic plasticity, and yet compared with other eukaryotes or bacteria, little is known about the design principles. We generated an extensive catalog of nascent and steady-state transcripts in Arabidopsis thaliana seedlings...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1603217113

    authors: Hetzel J,Duttke SH,Benner C,Chory J

    更新日期:2016-10-25 00:00:00

  • p85α deficiency protects β-cells from endoplasmic reticulum stress-induced apoptosis.

    abstract::In insulin resistant states such as type 2 diabetes, there is a high demand on the β-cell to synthesize and secrete insulin, which challenges the ability of the endoplasmic reticulum (ER) to synthesize and fold nascent proteins. This creates a state of ER stress that triggers a coordinated program referred to as the u...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1322564111

    authors: Winnay JN,Dirice E,Liew CW,Kulkarni RN,Kahn CR

    更新日期:2014-01-21 00:00:00

  • Ecological and socioeconomic effects of China's policies for ecosystem services.

    abstract::To address devastating environmental crises and to improve human well-being, China has been implementing a number of national policies on payments for ecosystem services. Two of them, the Natural Forest Conservation Program (NFCP) and the Grain to Green Program (GTGP), are among the biggest programs in the world becau...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.0706436105

    authors: Liu J,Li S,Ouyang Z,Tam C,Chen X

    更新日期:2008-07-15 00:00:00

  • Semaphorin 3A growth cone collapse requires a sequence homologous to tarantula hanatoxin.

    abstract::Axonal guidance is key to the formation of neuronal circuitry. Semaphorin 3A (Sema 3A; previously known as semaphorin III, semaphorin D, and collapsin-1), a secreted subtype of the semaphorin family, is an important axonal guidance molecule in vitro and in vivo. The molecular mechanisms of the repellent activity of se...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.23.13501

    authors: Behar O,Mizuno K,Badminton M,Woolf CJ

    更新日期:1999-11-09 00:00:00