Identifying stem cells and controlling osmotic shock

From materials to neuroscience and much much more - latest news from the Nature journals 27 November 2011

This press release contains:

---Summaries of newsworthy papers:

Biotechnology: Genetic changes in cultured ES cells

Medicine: Using patient iPS cell-derived neurons to learn about autism

Cell Biology: Identifying potential adult stem cells

Genetics: Variants associated multiple myeloma

Neuroscience: Mouse model of Rett Syndrome

Materials: Collective osmotic shock

---Mention of papers to be published at the same time with the same embargo

---Geographical listing of authors

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[1] Biotechnology: Genetic changes in cultured ES cells
DOI: 10.1038/nbt.2051

The largest study to date on the genetic stability of cultured human embryonic stem cells (hESCs) is published this week in Nature Biotechnology. The analysis of 125 ethnically diverse hESC lines originating from 38 laboratories around the world sheds light on the question of whether genetic mutations in the cells are related to the nature of the cells themselves or to the techniques used to grow them in culture.

HESCs show promise for cell therapy because in principle they can be converted into any cell type in the body and because they are able to grow and divide indefinitely in the laboratory. But during long-term culture, the cells can acquire genetic mutations, and some of these mutations could compromise the cells’ utility for regenerative medicine. It is believed that mutations that arise and endure over long-term culture provide a selective advantage for the cells, such as a greater propensity for self renewal.

Peter W Andrews and colleagues at the International Stem Cell Initiative carried out genetic analysis of a broad range of hESC lines at early and late stages of culture. Although most of the mutations they identified seemed to occur randomly, about 20% of the cell lines acquired amplifications of a specific region in chromosome 20. This region contains three genes, and one of them, BCL2L1, proved to be a strong candidate for driving hESC culture adaptation. The data generated in this study will be useful for understanding the frequency and types of genetic changes affecting cultured hESCs, an important issue in evaluating the cells for potential therapeutic applications.

Author contact:

Peter W Andrews (University of Sheffield, UK)
Tel: +44 114 222 4173; E-mail: [email protected]

Please note that this author is travelling and may be best contacted through his PA:

Nick Childs (University of Sheffield, UK)
Tel: +44 114 222 1083


[2] Medicine: Using patient iPS cell-derived neurons to learn about autism
DOI: 10.1038/nm2576

Individuals with Timothy syndrome, a neurodevelopmental disease, have changes in their cortical neuron fate and neurotransmitter expression, reports a paper published this week in Nature Medicine. These findings may begin to explain the neural mechanisms that underlie this disorder.

Timothy syndrome includes autism-like features and is caused by mutations in a calcium channel that leads to its over-activation.

Ricardo Dolmetsch and colleagues generate induced pluripotent stem cell-derived neurons from individuals with Timothy and compared them iPS-derived neurons from normal control individuals. The researchers found that iPS cell-derived neurons from Timothy syndrome patients had reduced expression of markers characteristic of cortical neurons that project to other areas of the cortex through the corpus callosum—the thick array of axons that connect the two lobes of the cortex together. Timothy syndrome-derived neurons also increased their generation of the neurotransmitters norepinephrine and dopamine due to a rise in the expression of the enzyme responsible for their production. The increase in the enzyme’s expression could be prevented by a calcium channel blocker.

Future studies are needed to determine how these changes in the brain would lead to autism-like phenotypes in individuals with Timothy syndrome.

Author contact:

Ricardo Dolmetsch (Stanford University, CA, USA)
Tel: +1 650 799 5497; E-mail: [email protected]


[3] Cell Biology: Identifying potential adult stem cells
DOI: 10.1038/ncb2384

A method based on counting single molecules in cells within an organism, helping to identify adult stem cells in tissues during homeostasis, ageing and regeneration, is reported online this week in Nature Cell Biology.

Using a fluorescence-based method, Alexander van Oudenaarden and colleagues monitor the RNA transcripts of several genes previously associated with stem cell function in the mouse intestine, a tissue that actively regenerates in mammals throughout adult life. They find that transcripts of genes previously thought to mark distinct cells with specific proliferative and regenerative properties actually have overlapping expression and are found in the same cells. They also identify changes in the spatial expression of some molecular markers following tissue injury, indicating the potential involvement of the corresponding cells in regeneration; this is a hypothesis that will require further testing.

This method should help researchers identify adult stem cells with regenerative properties in other mouse tissues, if complemented with functional approaches. Further work will be needed to discover whether this approach is transferable to human tissues.

Author contact:

Alexander van Oudenaarden (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 253 4446; E-mail: [email protected]


[4] Genetics: Variants associated multiple myeloma
DOI: 10.1038/ng.993

Genetic variants associated with multiple myeloma are reported this week in Nature Genetics.

Multiple myeloma is a cancer of the plasma cells in bone marrow, leading to formation of bone tumors. It is the second most common hematological malignancy, and is found more commonly in men and individuals over 65 years of age.

Richard Houlston and colleagues report a genome-wide association study in 1,675 individuals with multiple myeloma and 5,903 healthy controls, including studies from the UK and Germany. They identify two genomic regions associated with risk. This suggests pathways that may be involved in susceptibility to multiple myeloma.

Author contact:

Richard Houlston (Institute of Cancer Research, Surrey, UK)
Tel: +44 208 7224175; E-mail: [email protected]


[5] Neuroscience: Mouse model of Rett Syndrome
DOI: 10.1038/nn.2997

Mice engineered to contain a genetic mutation commonly found in Rett syndrome show symptoms associated with the disease, reports a study published online this week in Nature Neuroscience.

Rett syndrome is a type of autism spectrum disorder that is associated with mutations in a gene called methyl-CpG binding protein 2 (MeCP2). Although individuals with Rett mutations develop normally in the first two years of life, they fail to develop normal language and motor skills, and have breathing and cognitive difficulties.

Zhaolan Zhou and colleagues engineered a mouse line that contains this single MeCP2 mutation. The mice subsequently displayed similar developmental delays and locomotor and breathing abrnormalities seen in Rett patients. They also showed abnormal neurophysiological responses, cognitive impairments and anxiety-like behaviour, suggested that this may provide a good model system to study the neuronal basis of this disorder.

Author contact:

Zhaolan Zhou (University of Pennsylvania, PA, USA)
Tel: +1 215 746 5025; E-mail: [email protected]


[6] Materials: Collective osmotic shock
DOI: 10.1038/nmat3179

Soft materials permeable to solvents — such as cells or vesicles — can rupture as a result of stress build-up stemming from an imbalance in osmotic pressure. Such an osmotic burst has now been multiplied in a coordinated fashion within ordered materials, reports a study in Nature Materials this week. The approach leads to orderly nanoperforated materials that may find applications in photonics, optoelectronics and nanofiltration.

To prepare a material for such ‘collective osmotic shock’, Easan Sivaniah and colleagues used self-assembled block-copolymer films consisting of close-packed layers of polymethyl methacrylate (PMMA) globules within a polystyrene matrix. They then broke the globular PMMA down into oligomers using ultraviolet light, and immersed the films in acetic acid — a solvent suitable for the oligomers. As the solvent permeated through the film layer by layer, it swelled the oligomer globules, causing them to deform and rupture in concert. The researchers claim that such a collective osmotic rupture produces periodic nanoporosity within any ordered material containing a minority component that can be selectively degraded and solvated within a deformable matrix. The team demonstrated that these perforated structures behave as one-dimensional photonic crystals, and that they can be used as ultrafiltration membranes and as electrodes in light emitting devices.

Author contact:

Easan Sivaniah (Cambridge University, UK)
Tel: +44 1223 337267; E-mail: [email protected]


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


[7] An equilibrium-dependent retroviral mRNA switch regulates translational recoding
DOI: 10.1038/nature10657

[8] Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket
DOI: 10.1038/nature10641

[9] GlcNAcylation of histone H2B facilitates its monoubiquitination
DOI: 10.1038/nature10656

[10] Response to self antigen imprints regulatory memory in tissues
DOI: 10.1038/nature10664

[11] Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing
DOI: 10.1038/nature10672

[12] Structure of a methyl-coenzyme M reductase from Black Sea mats that oxidize methane anaerobically
DOI: 10.1038/nature10663


[13] Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells
DOI: 10.1038/nbt.2052


[14] Defining human ERAD networks through an integrative mapping strategy
DOI: 10.1038/ncb2383


[15] Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes
DOI: 10.1038/nchembio.721

[16] Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding
DOI: 10.1038/nchembio.733


[17] Hydrolytic catalysis and structural stabilization in a designed metalloprotein
DOI: 10.1038/nchem.1201

[18] Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity
DOI: 10.1038/nchem.1206


[19] Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina–associated domains
DOI: 10.1038/ng.969


[20] Influence of Atlantic meridional overturning circulation on the East Asian winter monsoon
DOI: 10.1038/ngeo1326

[21] Role of the deep mantle in generating the compositional asymmetry of the Hawaiian mantle plume
DOI: 10.1038/ngeo1328

[22] Arsenic sequestration by organic sulphur in peat
DOI: 10.1038/ngeo1329

[23] Origin of Indian Ocean Seamount Province by shallow recycling of continental lithosphere
DOI: 10.1038/ngeo1331


[24] Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses

[25] Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner


[26] H-atom relay reactions in real space
DOI: 10.1038/nmat3176


[27] Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease
DOI: 10.1038/nm.2490


[28] Decoding cell lineage from acquired mutations using arbitrary deep sequencing
DOI: 10.1038/nmeth.1781

[29] Optical recording of action potentials in mammalian neurons using a microbial rhodopsin
DOI: 10.1038/nmeth.1782


[30] Electrical contacts to one- and two-dimensional nanomaterials
DOI: 10.1038/nnano.2011.196


[31] Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene
DOI: 10.1038/nn.2989


[32] Nanoscale spectroscopy with polarized X-rays by NEXAFS-TXM
DOI: 10.1038/nphoton.2011.268

Nature PHYSICS (

[33] Coherent control of three-spin states in a triple quantum dot
DOI: 10.1038/nphys2149

[34] Topological semimetal in a fermionic optical lattice
DOI: 10.1038/nphys2134


[35] The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks
DOI: 10.1038/nsmb.2188

[36] Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors
DOI: 10.1038/nsmb.2189



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.

Canberra: 24
Clayton: 1
Fitzroy: 1
Parkville: 1, 24
Sydney: 1, 23

Antwerp: 32
Brussels: 1

Sao Paulo: 1

Ottawa: 33
Sherbrooke: 33
Toronto: 1
Vancouver: 21

Beijing: 34
Hunan: 1
Qingdao: 20
Shanghai: 1
Xi’an: 20

Brno: 1, 18
Prague: 1

Helsinki: 1
Tampere: 1

Grenoble: 11
Nantes: 32
Paris: 27

Berlin: 26, 32
Bonn: 4
Cologne: 35
Essen: 4
Frankfurt: 12
Hannover: 12
Heidelberg: 4, 11
Kiel: 23
Marburg: 12, 15

Bangalore: 1

Tehran: 1

Jerusalem: 1
Tel Aviv: 1

Milan: 36

Kawaguchi: 1
Kyoto: 1, 11, 26
Osaka: 8
Saitama: 9, 12
Sendai: 26
Tokushima: 2
Tokyo: 1, 9
Toyama: 26

Gouda: 19
Leiden: 1, 19, 35
Utrecht: 3

Doha: 6

Moscow: 1

Singapore: 1

Ljubljana: 32

Seoul: 1

Madrid: 36
San Sebastian: 26
Seville: 6

Gothenburg: 1
Malmo: 4
Stockholm: 1, 35

Freibourg: 1
Geneva: 1
Zurich: 22

Bath: 18
Birmingham: 17, 25
Cambridge: 6
Cardiff: 1
Coventry: 18
Edinburgh: 1
Leeds: 4
London: 1, 24
Manchester: 1
Newcastle: 1, 4, 27
Nottingham: 1
Oxford: 4, 14, 24
Roslin: 1
Salisbury: 4
Sheffield: 1
South Mimms: 1
Surrey: 4


Berkeley: 6, 31
La Jolla: 14
Livermore: 30
Los Angeles: 1, 2, 19
Menlo Park: 14
San Francisco: 1, 10
Stanford: 1, 2, 14


Boulder: 20
New Haven: 1, 25

Athens: 1

Honolulu: 21

Chicago: 1

West Lafayette: 34
Baltimore: 13
Gaithersburg: 30

Amherst: 21
Boston: 1, 5, 9, 13, 14, 25
Cambridge: 3, 7, 13, 27, 29
Worcester: 10

Ann Arbor: 17
St Louis: 15

New Jersey
Nutley: 1

New York
Flushing: 24
New York: 1, 7, 9, 10, 11, 13, 31
Saranac Lake: 25

North Carolina
Chapel Hill: 28
Research Triangle: 16

Portland: 28

Philadelphia: 5

Rhode Island
Providence: 20

Dallas: 16

Seattle: 28

Madison: 1



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Tel: +44 20 7843 4658; E-mail: [email protected]

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Published: 28 Nov 2011

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