Research Highlights |
Featured
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News |
GlaxoSmithKline strikes back over anti-ageing pills
Drugs do work as thought, says pharmaceutical giant.
- Ewen Callaway
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Letter |
Comprehensive methylome map of lineage commitment from haematopoietic progenitors
During haematopoiesis, multipotent progenitors differentiate into progressively restricted myeloid or lymphoid progenitors. A comprehensive genome-wide DNA methylation analysis of haematopoietic cell populations with well-characterized differentiation potentials reveals remarkable epigenetic plasticity during lymphoid and myeloid restriction.
- Hong Ji
- , Lauren I. R. Ehrlich
- & Andrew P. Feinberg
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Article |
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
The identity of the cells that form the haematopoietic stem cell (HSC) niche in bone marrow has been unclear. These authors identify nestin-expressing mesenchymal stem cells as niche-forming cells. These nestin-expressing cells show a close physical association with HSCs and express high levels of genes involved in HSC maintenance, and their depletion reduces bone marrow homing of haematopoietic progenitors.
- Simón Méndez-Ferrer
- , Tatyana V. Michurina
- & Paul S. Frenette
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Letter |
Production of p53 gene knockout rats by homologous recombination in embryonic stem cells
The rat is a animal model widely used for studying human physiology and disease, but functional genomics and genetic research have been stifled by the limited availability of gene targeting tools. These authors have established gene targeting by homologous recombination in rat embryonic stem cells, and have generated p53 gene knockout rats for the first time.
- Chang Tong
- , Ping Li
- & Qi-Long Ying
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News |
Muscling in on limb regeneration
Researchers pin down a pathway coming between mammals and the ability to regenerate tissue salamander-style.
- Alla Katsnelson
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News |
Skin cells converted to heart muscle cells
Cell identity switched in mice without the use of stem cells.
- Heidi Ledford
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Article
| Open AccessThe Amphimedon queenslandica genome and the evolution of animal complexity
These authors report and analyse the draft genome sequence of the demosponge Amphimedon queenslandica. Sponges lie on the earliest branching lineage in the animal kingdom and thus have been important in studies of the origins of multicellularity. Comparative genomic analyses presented here provide significant insights into evolutionary origins of genes and pathways related to the hallmarks of metazoan multicellularity and to cancer biology.
- Mansi Srivastava
- , Oleg Simakov
- & Daniel S. Rokhsar
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Letter |
Rb regulates fate choice and lineage commitment in vivo
The retinoblastoma tumour suppressor protein pRb can suppress the activity of certain transcription factors and potentiate the activity of others, and has been shown to affect the differentiation of different cell lineages in vitro. These authors show that the Rb gene has a role in driving bone cell formation or brown adipose tissue formation in vivo.
- Eliezer Calo
- , Jose A. Quintero-Estades
- & Jacqueline A. Lees
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News |
UK embryo agency faces the axe
Coalition government promises to abolish respected regulator in effort to cut back on quangos.
- Daniel Cressey
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News |
Mouse pain study stirs debate
Canadian scientists vindicated after being accused of mistreating laboratory animals.
- Janelle Weaver
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Letter |
Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca2+ channel
An electrical gradient is crucial for the normal functioning of the heart. These authors show that Wnt11 signals are required to set up this gradient in the developing zebrafish heart by regulating the L-type calcium channel.
- Daniela Panáková
- , Andreas A. Werdich
- & Calum A. MacRae
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Brief Communications Arising |
Segregation of yeast nuclear pores
- Anton Khmelinskii
- , Philipp J. Keller
- & Michael Knop
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Research Highlights |
Molecular evolution: Sperm-making origins
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News |
Marmots fatten up on climate change
Rodent population boom linked to bigger bellies and longer summers.
- Lucas Laursen
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Article |
Epigenetic memory in induced pluripotent stem cells
Pluripotent stem cells can be generated in the laboratory through somatic cell nuclear transfer (generating nuclear transfer embryonic stem cells, ntESCs) or transcription-factor-based reprogramming (producing induced pluripotent stem cells, iPSCs). These methods reset the methylation signature of the genome — but to what extent? Here it is found that mouse iPSCs 'remember' the methylation status of their tissue of origin, but the methylation of ntESCs is more similar to that of naturally produced ES cells.
- K. Kim
- , A. Doi
- & G. Q. Daley
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Letter |
Cross-species genomics matches driver mutations and cell compartments to model ependymoma
Ependymoma is a type of neural tumour that arises throughout the central nervous system. Using comparative transcriptomics in mouse and human tumours, these authors home in on mutations that are specific to individual tumour subgroups. In doing so, they generate the first mouse model of ependymoma and demonstrate the power of interspecific genomic comparisons to interrogate cancer subgroups.
- Robert A. Johnson
- , Karen D. Wright
- & Richard J. Gilbertson
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Letter |
Regulation of myeloid leukaemia by the cell-fate determinant Musashi
Chronic myelogenous leukaemia (CML) can progress from a chronic to an acute phase. These authors show in mouse models that leukaemia progression is controlled by the cell-fate regulator Musashi2, which in turn regulates Numb, Notch and p53 to block cellular differentiation. Musashi2 expression can be increased by aberrant transcription factors found in leukaemia, is observed during cancer progression in human CML patients and is associated with poorer prognosis.
- Takahiro Ito
- , Hyog Young Kwon
- & Tannishtha Reya
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News |
Mystery RNA spawns gene-activating peptides
Short peptides that regulate fruitfly development are produced from 'junk' RNA.
- Heidi Ledford
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Research Highlights |
Stem cells: Blood source
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Letter |
Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development
PHF8 is a JmjC domain-containing protein, the gene for which has been linked to X-linked mental retardation (XLMR). These authors demonstrate PHF8 to be a histone demethylase with activity against H4K20me1. It has a role in regulating gene expression as well as in neuronal cell survival and craniofacial development in zebrafish. The results suggest there may be a link between histone methylation dynamics and XLMR.
- Hank H. Qi
- , Madathia Sarkissian
- & Yang Shi
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Letter |
A random cell motility gradient downstream of FGF controls elongation of an amniote embryo
Most animal embryos grow through cell accumulation in a posterior growth zone, but the underlying forces are unknown. It is now proposed that posterior elongation in chicken embryos is an emergent property that arises from graded cell motility in random directions (as opposed to directed movement). This occurs in response to signalling through the fibroblast growth factor.
- Bertrand Bénazéraf
- , Paul Francois
- & Olivier Pourquié
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Letter |
Mechanism and regulation of acetylated histone binding by the tandem PHD finger of DPF3b
The lysine residues of histone proteins can be acetylated or methylated, with important effects on gene expression. Until recently the protein modules that bind acetyl-lysine have been limited to bromodomains. However, the tandem plant homeodomain (PHD) finger of human DPF3b — which is involved in gene activation — has also been reported to bind to acetylated histones. Here, three-dimensional solution structures of DPF3b offer mechanistic insight into how this protein recognizes acetylation marks.
- Lei Zeng
- , Qiang Zhang
- & Ming-Ming Zhou
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Letter |
A new DAF-16 isoform regulates longevity
The insulin/IGF-1 signalling (IIS) pathway is involved in various biological processes, including regulation of longevity. In the worm Caenorhabditis elegans, the transcription factor DAF-16a, one of two isoforms, has a major role in this pathway, regulating longevity, stress response and dauer diapause. These authors describe a new isoform, DAF-16d/f, which is also important in the regulation of lifespan. The DAF-16 isoforms functionally cooperate to fine-tune IIS-mediated processes in the context of a whole organism.
- Eun-Soo Kwon
- , Sri Devi Narasimhan
- & Heidi A. Tissenbaum
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News |
Genetic variations offer longer life
Many centenarians carry particular genetic signatures.
- Heidi Ledford
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Letter |
Spatiotemporal regulation of cell-cycle genes by SHORTROOT links patterning and growth
In higher animals and plants, the processes of growth and patterning are coordinated. In this study, the authors study patterning in Arabidopsis root and show that two key regulators of root organ patterning directly control the transcription of specific components of the cell-cycle machinery. This study provides a direct link between developmental regulators, components of the cell-cycle machinery and organ patterning.
- R. Sozzani
- , H. Cui
- & P. N. Benfey
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Letter |
Co-option of the hormone-signalling module dafachronic acid–DAF-12 in nematode evolution
Plants or animals with identical genomes in a given species can develop into wildly differing forms, depending on environmental conditions, a phenomenon that is widespread in nature yet rarely described in genetic and molecular terms. These authors show that the formation of additional teeth-like structures in the mouth of the nematode Pristionchus pacificus in response to overcrowding is mediated by the same endocrine system that controls dauer larva formation.
- Gilberto Bento
- , Akira Ogawa
- & Ralf J. Sommer
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Brief Communications Arising |
Conrad et al. reply
- Sabine Conrad
- , Markus Renninger
- & Thomas Skutella
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Brief Communications Arising |
Human adult germline stem cells in question
- Kinarm Ko
- , Marcos J. Araúzo-Bravo
- & Hans R. Schöler
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Letter |
Hormonal control of the shoot stem-cell niche
- Zhong Zhao
- , Stig U. Andersen
- & Jan U. Lohmann
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News |
How fins became limbs
Four-legged creatures may have gained a foothold by ditching genes guiding fin development.
- Janelle Weaver
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Letter |
Loss of fish actinotrichia proteins and the fin-to-limb transition
One of the steps in the evolution of tetrapod limbs was the loss of the distinctive fringe of fin rays and fin folds found in the fins of fishes. It is now shown that two novel proteins, actinodin 1 and 2, are essential structural components of fin rays and fin folds in zebrafish, and are also encoded in the genomes of other teleost fish and at least one species of shark, but not in tetrapods. It is suggested that the loss of these genes may have contributed to the fin-to-limb transition in tetrapod evolution.
- Jing Zhang
- , Purva Wagh
- & Marie-Andrée Akimenko
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Letter |
Planar cell polarity breaks bilateral symmetry by controlling ciliary positioning
During vertebrate development, the dorsal–ventral and anterior–posterior (A–P) body axes are determined first, after which left–right (L–R) asymmetry is established. But the molecular mechanism by which L–R symmetry is broken in reference to the other two axes is poorly understood. Here it is shown that two mouse genes, Vang1 and Vang2, which belong to the planar cell polarity family, are required to interpret the A–P patterning information and link it to L–R asymmetry.
- Hai Song
- , Jianxin Hu
- & Yingzi Yang
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Letter |
Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans
It is shown here that the methylation of histone proteins regulates lifespan in Caenorhabditis elegans. Deficiencies in members of the ASH-2 complex, which trimethylates histone H3 at lysine 4 (H3K4), extend worm lifespan. Meanwhile, the H3K4 demethylase RBR-2 is required for normal lifespan. These findings are consistent with the idea that an excess of H3K4 trimethylation reduces longevity. The extension of lifespan caused by ASH-2 deficiency requires an intact adult germline and the continuous production of mature eggs.
- Eric L. Greer
- , Travis J. Maures
- & Anne Brunet
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News |
A wake-up call for dozing Drosophila
Association study shows that the genetics of sleep are as complex in flies as in humans.
- Virginia Hughes
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Letter |
Progesterone induces adult mammary stem cell expansion
Reproductive history influences breast cancer risk but the cellular mechanisms are unclear. Here it is shown that ovarian hormones regulate the size of the mammary stem cell pool in mice. The size of this pool increases when progesterone levels increase during the reproductive cycle. Progesterone probably regulates stem cell numbers through a paracrine mechanism involving induction of RANKL and Wnt in luminal cells.
- Purna A. Joshi
- , Hartland W. Jackson
- & Rama Khokha
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Letter |
Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
Using a mouse model of Mycobacterium avium infection, it is shown here that interferon-γ regulates the proliferation of primitive haematopoietic cells during chronic infection.
- Megan T. Baldridge
- , Katherine Y. King
- & Margaret A. Goodell
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News & Views |
Cues from steroid hormones
The steroid hormones oestrogen and progesterone have a role in sickness and in health. In breast tissue, both roles probably work through a single mechanism: controlling the number and activity of mammary stem cells.
- John P. Lydon
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Review Article |
Nuclear reprogramming to a pluripotent state by three approaches
- Shinya Yamanaka
- & Helen M. Blau
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Letter
| Open AccessThe Ectocarpus genome and the independent evolution of multicellularity in brown algae
The genome of Ectocarpus siliculosis, a model for the study of brown algae, has been sequenced. These seaweeds are complex photosynthetic organisms that have adapted to rocky coastal environments. Genome analysis sheds light on this adaptation, revealing an extended set of light-harvesting and pigment biosynthesis genes, and new metabolic processes such as halide metabolism. Comparative analyses are also significant with respect to the evolution of multicellularity in plants, animals and brown algae.
- J. Mark Cock
- , Lieven Sterck
- & Patrick Wincker
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Letter |
Phenotypic robustness conferred by apparently redundant transcriptional enhancers
Transcriptional enhancers are segments of regulatory DNA located some distance from the coding region of a gene, and several of them may sometimes serve apparently redundant functions. These authors demonstrate in Drosophila that such 'redundant' enhancers, by contributing higher overall levels of transcription, ensure robustness of phenotypes against both genetic and environmental perturbations, for example mutations in other genes or temperature changes that would otherwise lead to aberrant development.
- Nicolás Frankel
- , Gregory K. Davis
- & David L. Stern
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Letter |
Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis
The protein ephrin-B2 is known to be upregulated during angiogenesis — the growth of new blood vessels — but its precise function has been unclear. Here it is shown that signalling through ephrin-B2 controls vessel sprouting. Mechanistically, ephrin-B2 seems to function in part by regulating the internalization of vascular endothelial growth factor receptors (VEGFRs). The results indicate that blocking ephrin-B2 signalling might be an alternative to blocking VEGFR function to disrupt angiogenesis in tumours.
- Yingdi Wang
- , Masanori Nakayama
- & Ralf H. Adams
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Research Highlights |
Cancer: Melanoma's moving target
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News |
Mice pull pained expressions
Animal and human faces display similar responses to suffering.
- Janelle Weaver
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Letter |
Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis
The protein ephrin-B2 is known to be upregulated during angiogenesis — the growth of new blood vessels — but its precise function has been unclear. Here it is shown that signalling through ephrin-B2 controls vessel sprouting. Mechanistically, ephrin-B2 seems to function in part by regulating the internalization of vascular endothelial growth factor receptors (VEGFRs). The results indicate that blocking ephrin-B2 signalling might be an alternative to blocking VEGFR function to disrupt angiogenesis in tumours.
- Suphansa Sawamiphak
- , Sascha Seidel
- & Amparo Acker-Palmer
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