Stem cells: Turning off ‘stemness’ in skin cells

Summaries of newsworthy papers: Biogeography- Cosmopolitan phages, The not-so-sweet side of malaria, An atomic force pencil, Let there be light, Genetic variants predisposing to coeliac disease, Mitochondrial DNA deletions affect lifespan, Smokers insensitive to what might have been, Bone marrow nurturers, Altered stem cells accelerate ageing ...


For papers that will be published online on 02 March 2008
This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:
Stem cells: Turning off ‘stemness’ in skin cells - Nature
Biogeography: Cosmopolitan phages - Nature
The not-so-sweet side of malaria - Nature Chemical Biology
An atomic force pencil - Nature Materials
Let there be light - Nature Nanotechnology
Genetic variants predisposing to coeliac disease - Nature Genetics
Mitochondrial DNA deletions affect lifespan - Nature Genetics
Smokers insensitive to what might have been - Nature Neuroscience
Bone marrow nurturers - Nature Immunology
Altered stem cells accelerate ageing - Nature Cell Biology
Chemical treatment of neurons makes them light sensitive - Nature Methods

· Mention of papers to be published at the same time with the same embargo
· Geographical listing of authors

PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of Press contacts for the Nature journals are listed at the end of this release.

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********************************** NATURE ************************************

[1] Stem cells: Turning off ‘stemness’ in skin cells

DOI: 10.1038/nature06642

Maintaining healthy skin depends on the self-renewing capacity of stem cells deep within the skin’s innermost layer. Cells originating from these stem cells proliferate and embark on a differentiation programme as they migrate towards the outer layers, which terminates as they near the skin’s surface. A paper published online by Nature has discovered the switch mechanism responsible for imposing the molecular boundary between the proliferating basal cells and terminally differentiating outer skin cells.

MicroRNAs are small RNAs that do not encode proteins themselves, but which help to regulate the expression of other genes. Elaine Fuchs and her colleagues have identified a particular microRNA - called miR-203 - that stimulates the differentiation of epidermal stem cells. miR-203 is not expressed in epidermal stem cells, but it is made as cells commit to differentiate. It enforces differentiation by suppressing the production of p63, a protein that drives cell proliferation, thereby inducing the cells to stop dividing.

By this action, miR-203 ensures that the various layers of the skin retain their proper identities.

Author contact:
Elaine Fuchs (The Rockefeller University, New York, NY, USA)
Tel: +1 212 327 7953; E-mail: [email protected]

[2] Biogeography: Cosmopolitan phages

DOI: 10.1038/nature06735

Viruses and bacterial viruses (known as phages) are among the most abundant life forms on the planet. A paper in this week’s Nature analyses the geographical distribution of viral communities in modern organosedimentary structures known as microbialites, the living analogues of the oldest fossils on Earth, and comes up with some surprising nuggets of information.

Microbialites first appeared in the geological record, 3.5 billion years ago, and for more than 2 billion years they are the main evidence of life on Earth

Christelle Desnues and colleagues use comparative metagenomics to show that phages associated with such structures are very different not only from each other but also from those found in any other ecosystem so far.

The team’s findings indicate that modern microbialites are endemic remnants of ancient ecosystems.

Author contact:
Christelle Desnues (San Diego State University, CA, USA)
Tel: +1 619 594 1336; E-mail: [email protected]

Other papers from Nature to be published online at the same time and with the same embargo:

[3] Localization and functionality of microsporidian iron-sulphur cluster assembly proteins
DOI: 10.1038/nature06606

************************** NATURE CHEMICAL BIOLOGY ************************

[4] The not-so-sweet side of malaria

DOI: 10.1038/nchembio.75

A chip that can be used to understand how people respond to toxic malarial sugars is described in a paper published online this week in Nature Chemical Biology. The chip, and the information it provides, could be used to aid future efforts in creating effective antimalarial vaccines.

The malarial parasite, Plasmodium falciparum, makes a large amount of sugars called GPIs. Rather than being ‘sweet’, these GPI sugars are quite toxic, and a vaccine against them could protect people from getting malaria. However, because it is not easy to obtain pure samples of these complicated sugars, it has been difficult to determine exactly which GPI sugars might be most useful for a vaccine.

Using very pure samples made chemically, Peter Seeberger and colleagues attached malarial GPI sugars to a glass slide to create a GPI chip. Using this chip, the authors looked at the antibodies that were made by people before and after exposure to malaria. After malarial exposure, people had more antibodies to only very specific GPI sugars.

Author contact:
Peter Seeberger, (Swiss Federal Institute of Technology (ETH) Zurich, Switzerland)
Tel: +41 44 633 2103, E-mail: [email protected]

Other papers from Nature Chemical Biology to be published online at the same time and with the same embargo:

[5] Progressive ordering with decreasing temperature of the phospholipids of influenza virus
DOI: 10.1038/nchembio.77

********************************* NATURE MATERIALS ******************************

[6] An atomic force pencil

DOI: 10.1038/nmat2136

A method of creating electrically conductive paths at the nanoscale is reported online this week in Nature Materials. Given the small dimensions of these paths, this could lead to the development of devices for ultrahigh-density information storage and processing.

Jeremy Levy and colleagues took advantage of the fact that the interface between two insulating layers of perovskite crystals can be highly conductive under appropriate conditions. They applied a high voltage to the tip of an atomic force microscope, and used this to induce conductive paths - suitable for carrying electrical information - that are only a few nanometres wide. The tip can be seen as a pencil for drawing nanoscale electric circuits on a writing board represented by the interface.

Author contact:
Jeremy Levy (University of Pittsburgh, Pittsburgh, PA, USA)
Tel: +1 412 624 2736; E-mail: [email protected]

Other papers from Nature Materials to be published online at the same time and with the same embargo:

[7] Strain control and spontaneous phase ordering in vertical nanocomposite heteroepitaxial thin films
DOI: 10.1038/nmat2124

************************* NATURE NANOTECHNOLOGY************************

[8] Let there be light

DOI: 10.1038/nnano.2008.7

The light emitted by silicon nanocrystals comes mostly from defects within the nanocrystals, according to a paper published online this week in Nature Nanotechnology. Silicon dominates the electronics industry, but other semiconductor materials with better optical properties are preferred for applications in photonics. Until now the way in which silicon emits light has been a bit of a mystery, frustrating efforts to exploit it in optical applications.

Manus Hayne and co-workers investigated whether the light emitted by tiny crystals of silicon embedded in silicon dioxide came from defects or was due to quantum effects confining particles inside the nanocrystals. By measuring the emission of light when their silicon samples were placed in a strong magnetic field, they were able to show that the light emission was dominated by defects.

The team then exposed the silicon to hydrogen, which made the defects inactive, and the nature of the light changed to reflect the fact that quantum-confinement effects were responsible for the emission. Subsequently, when the silicon was exposed to ultraviolet light to remove the hydrogen, the defects reappeared and dominated the light emission again. As photons replace electrons in various devices, a better understanding of the optical properties of silicon could allow it to compete with other materials.

Author contact:
Manus Hayne (University of Lancaster, UK)
Tel: +44 1524 593 279; E-mail: [email protected]

Ulrich Gösele (Max Planck Institute for Microstructure Physics, Halle, Germany) N&V author
Tel: +49 345 5582 657; E -mail: [email protected]

Other papers from Nature Nanotechnology to be published online at the same time and with the same embargo:

[9] Nanoparticle-mediated cellular response is size-dependent

[10] Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications

[11] Controlled cobalt doping of magnetosomes in vivo (N&V)

******************************** NATURE GENETICS ****************************

[12] Genetic variants predisposing to coeliac disease

DOI: 10.1038/ng.102

Scientists have identified variants in seven genomic regions that predispose to coeliac disease. The research, published online in Nature Genetics, strengthen the idea that common factors predispose to a range of autoimmune disorders, such as coeliac disease and type 1 diabetes.

Coeliac disease is an autoimmune disorder of the small intestine that is caused by a reaction to a gluten protein found in wheat, rye and barley, requiring affected individuals to eat a gluten-free diet.

In a study last year, David van Heel and colleagues carried out a genome-wide association study of coeliac disease, and identified a region on chromosome 4 affecting risk. They have now analyzed additional candidate risk variants in individuals with and without the disease, and report seven new regions that are associated with susceptibility. Of the seven, six contain genes that control immune responses, and their identification refines knowledge of the specific immune pathways involved in the etiology of the disease.

Author contact:
David van Heel (Barts and the London School of Medicine and Dentistry, UK)
Tel: +44 207 882 2330; E-mail: [email protected]

[13] Mitochondrial DNA deletions affect lifespan

DOI: 10.1038/ng.95

Large DNA deletions in mitochondria - the energy-producing units of the cell - are associated with premature ageing in mice, according to a study published online this week in Nature Genetics.

A widely debated mitochondrial theory of ageing proposes that the lifelong accumulation of mitochondrial DNA mutations contributes to the decline of tissue function observed in ageing. Lawrence Loeb and colleagues studied so-called ‘mitochondrial mutator’ mice, which have a 500-times greater mutation burden than normal mice. They previously reported that single base-pair mutations in mitochondrial DNA are not associated with accelerated ageing; however, they now show that these prematurely aged mice have abundant large deletions in mitochondrial DNA, suggesting an important role for these lesions in the ageing process.

The effect of these deletions on mitochondrial function is different from tissue to tissue, which suggests that tissues are differentially susceptible to the effects of mitochondrial mutations.

Author contact:
Lawrence Loeb (University of Washington, Seattle, WA, USA)
Tel: +1 206 543 6015; E-mail: [email protected]

Other papers from Nature Genetics to be published online at the same time and with the same embargo:

[14] PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos
DOI: 10.1038/ng.99

[15] LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis
DOI: 10.1038/ng.98

[16] Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes
DOI: 10.1038/ng.101

********************************* NATURE NEUROSCIENCE ***************************

[17] Smokers insensitive to what might have been

DOI: 10.1038/nn2067

Chronic cigarette smokers consider the consequences of their choices differently than non-smokers according to a study in the April issue of Nature Neuroscience. In particular, smokers’ decisions are not influenced by the outcome that would have followed an alternative choice.

Read Montague and colleagues asked people to play a game in which they repeatedly decided how much of their money to invest in an artificial stock market. After each investment decision, the change in the market was revealed and the subjects found out how much money they won. The authors could predict subsequent choices for non-smokers based on the difference between the amount of money the subjects won and the amount of money they could have won by making the largest possible bet. In contrast, for smokers, this difference had little influence on their subsequent choices. This suggests that smokers may make poor decisions because they ignore alternative outcomes that could have been achieved.

Even though smokers and non smokers made different choices, brain activity measured during this task in all participants was correlated with the difference between what actually happened and what might have been. Thus, the authors conclude that smokers’ brains have information about what might have happened, but ignore it in deciding how to act.

Author contact:
Read Montague (Baylor College of Medicine, Houston, TX, USA)
Tel: +1 713 798 3134; Email: [email protected]

Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:

[18] Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter
DOI: 10.1038/nn2060

[19] TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation
DOI: 10.1038/nn2068

[20] Motor protein-dependent transport of AMPA receptors into spines during long-term potentiation
DOI: 10.1038/nn2063

********************************** NATURE IMMUNOLOGY ***************************

[21] Bone marrow nurturers

DOI: 10.1038/ni1571

Researchers have identified a new cell residing in bone marrow that provides an essential survival factor for antibody-producing B cells reports a study published online this week in Nature Immunology.

Bone marrow is an essential tissue at the site of all blood cell development; however, different sites within the marrow appear to support development or survival of specific types of blood cells. Steffen Jung and colleagues identified nurturing cells, called bone marrow-resident dendritic cells, or bmDCs, that reside in clusters that surround blood vessels in the marrow. Mature B cells return from the bloodstream and take up residence nestled close to the bmDCs. The bmDCs produce a factor called macrophage migration-inhibiting factor that the authors show is absolutely required for the B cell survival. Loss of the bmDCs led to simultaneous loss of the bone marrow B cells.

The new findings may lead to further research that has implications for B cell malignancies such as multiple myeloma, in which the tumour cells hijack the bone marrow, although further research into this area is required.

Author contact:
Steffen Jung (Weizmann Institute of Science, Rehovot, Israel)
Tel: +972 8 934 2787; E-mail: [email protected]

********************************* NATURE CELL BIOLOGY ****************************

[22] Altered stem cells accelerate ageing

DOI: 10.1038/ncb1708

Progerin, a mutant protein associated with both premature and normal ageing, acts by interfering with human mesenchymal stem cells (hMSCs). A study published online this week in Nature Cell Biology provides a mechanism by which this protein contributes to the premature ageing disease Hutchinson-Gilford Progeria Syndrome (HGPS), and implications for our understanding of normal ageing.

Progerin, an abnormal form of the nuclear protein lamin A, is the causal agent of HGPS. However, progerin is also produced in normal individuals, and its presence in healthy cells has been linked to normal ageing.

Paola Scaffidi and colleagues have found that high levels of progerin alter the identity of the stem cells, resulting in abnormal osteogenesis and adipogenesis, consistent with the defects seen in the HGPS disease. They also see that proteins in the Notch signalling pathway - known to be important for stem cell differentiation - are more active when progerin is present; blocking the Notch pathway can partly rescue the problems in the stem cells’ fate. The Notch pathway also seems to be affected in HSPS patient cells.

While providing a possible mechanism by which progerin contributes to the HGPS disease, these findings also have implications for our understanding of normal ageing and suggest that progerin effects on Notch signalling might similarly affect healthy hMSCs, and reduce potential for tissue homeostasis during ageing.

Author contact:
Paola Scaffidi (National Cancer Institute, NIH, Bethesda, MD, USA)
Tel: +1 301 435 2664; E-mail: [email protected]

********************************** NATURE METHODS ********************************

[23] Chemical treatment of neurons makes them light sensitive

DOI: 10.1038/nmeth.1187

A chemical treatment that makes neurons light responsive is described online this week in Nature Methods. This will allow researchers to selectively increase neuronal activity in animals. This is directly applicable to understanding the functioning of the nervous system and in the future it may have therapeutic applications.

Neuronal activity mediates behaviour in all animals with neurons but light doesn’t normally regulate this activity. Neuroscientists have developed artificial methods however, that allow them to control neuronal activity with light. Existing methods for imparting long-term light sensitivity to neurons requires expression of foreign proteins. This can be done with genetic engineering but is difficult and not always feasible.

To overcome this limitation Richard Kramer and colleagues designed a chemical that permanently attaches to cell surface proteins and acts as a ‘photoswitch’. Exposure to different colours of light flips the photoswitch between two different physical orientations. When the chemical is added to neurons it attaches to potassium channels on their surface and the light-induced flipping blocks and unblocks the channels to increase or decrease the excitability of the neurons.

This method will allow researchers to control the activity of almost any neuron by simply treating it with the chemical and shining light on the cell.

Author contact:
Richard H. Kramer (University of California, Berkeley, CA, USA)
Tel: +1 510 643 2406; E-mail: [email protected]

Other papers from Nature Methods to be published online at the same time and with the same embargo:

[24] Systematic identification of mammalian regulatory motifs target genes and functions
DOI: 10.1038/nmeth.1188

Items from other Nature journals to be published online at the same time and with the same embargo:


[25] Nanomechanical control of an optical antenna
DOI: 10.1038/nphoton.2008.27

[26] Observation of two-photon emission from semiconductors
DOI: 10.1038/nphoton.2008.28

Nature PHYSICS (

[27] Quantum interference of tunnel trajectories between states of different spin length in a dimeric molecular nanomagnet
DOI: 10.1038/nphys886

[28] Suprafroth in type-I superconductors
DOI: 10.1038/nphys888


[29] Transcription factor FOXO3a controls the persistence of memory CD4+ T cells during HIV infection
DOI: 10.1038/nm1728

[30] Protein kinase CK2 links extracellular growth factor signaling with the control of p27Kip1 stability in the heart
DOI: 10.1038/nm1729

[31] A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell–mediated suppression
DOI: 10.1038/nm1721

[32] The Notch pathway in podocytes plays a role in the development of glomerular disease
DOI: 10.1038/nm1731


[33] MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells
DOI: 10.1038/nsmb.1391

[34] A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl-2 dependent regulation of DNA methyltransferases
DOI: 10.1038/nsmb.1399

[35] GroEL stimulates protein folding through forced unfolding
DOI: 10.1038/nsmb.1394



The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Antwerp: 8
Leuven: 8

Montreal: 29
Toronto: 9, 30
Vancouver: 20, 35

Prague: 33

Helsinki: 15

Aubiere: 3
Grenoble: 11

Augsburg: 6
Berlin: 30
Freiburg: 8
Konstanz: 25
Marburg: 3
Tubingen: 15

Dublin: 12
Galway: 12

Haifa: 26
Rehovot: 21

Catanzaro: 10
Milan: 20

Kanagawa: 14

Mexico City: 2

Amsterdam: 12, 14
Groningen: 12
Leiden: 12
Utrecht: 12

Singapore: 2

Madrid: 34

Basel: 4, 14, 33
Zurich: 1, 4

Bristol: 12
Cambridge: 7, 12, 18
Derby: 12
Didcot: 11
Edinburgh: 11
Lancaster: 8
Leeds: 12
London: 12, 18
Newcastle: 3
Oxford: 4, 12
Sheffield: 12
Warrington: 11

Berkeley: 16, 23
La Jolla: 23, 27
Los Angeles: 23, 31
San Diego: 2, 29
San Francisco: 19
Santa Barbara: 2
District of Columbia
Washington: 6
Gainesville: 27
Miami: 2
Orlando: 27
St Petersburg: 2
Argonne: 2
Ames: 28
Bethesda: 5, 22, 32
Frederick: 24
Boston: 14, 15, 16, 24
Cambridge: 14, 24, 34
Albion: 28
Ann Arbor: 20
St Louis: 34
New Jersey
Princeton: 35
New Mexico
Los Alamos: 7
New York
Bronx: 32
Cold Spring Harbor: 34
New York: 1
Philadelphia: 34
Pittsburgh: 6
College Station: 7
Houston: 2, 10, 17, 31
Seattle: 13
Madison: 13


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Nature Chemical Biology (Boston)
Andrea Garvey
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Nature Genetics (New York)
Orli Bahcall
Tel: +1 212 726 9311; E-mail: [email protected]

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Alison Stoddart
Tel: +44 20 7843 4593; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
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Nature Methods (New York)
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Nature Nanotechnology (London)
Peter Rodgers
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Published: 02 Mar 2008

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