Research Highlights |
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Research Highlights |
Biology: Colour-blind
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News & Views |
Cell reprogramming gets direct
In a feat of biological wizardry, one type of differentiated cell has been directly converted into another, completely distinct type. Notably, the approach does not require a stem-cell intermediate stage.
- Cory R. Nicholas
- & Arnold R. Kriegstein
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News |
NIH may allow stem-cell lines from younger embryos
Lines derived from pre-blastocyst stage embryos could be eligible for agency funding.
- Meredith Wadman
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Letter |
Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice
Sequence variations in a 58-kilobase interval on human chromosome 9p21 have been associated with an increased risk of coronary artery disease. However, this interval contains no protein-coding genes and the mechanism underlying the increased risk has been unclear. Here, the corresponding interval has been deleted from mouse chromosome 4, revealing that this part of the chromosome regulates the cardiac expression of two nearby genes, Cdkn2a and Cdkn2b, and the proliferation dynamics of vascular cells.
- Axel Visel
- , Yiwen Zhu
- & Len A. Pennacchio
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Letter |
Rere controls retinoic acid signalling and somite bilateral symmetry
The vertebrate body plan shows marked bilateral symmetry, although this can be disrupted in conditions such as scoliosis. Here, a mutation in Rere is found that leads to the formation of asymmetrical somites in mouse embryos; furthermore, Rere is shown to control retinoic acid signalling, which is required to maintain somite symmetry by interacting with Fgf8. The results provide insight into how bilateral symmetry is maintained.
- Gonçalo C. Vilhais-Neto
- , Mitsuji Maruhashi
- & Olivier Pourquié
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Letter |
Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Here, iPS cell technology is used to study the mechanisms underlying dyskeratosis congenita in humans. Reprogramming restores telomere elongation in dyskeratosis congenita cells despite genetic lesions affecting telomerase. The reprogrammed cells were able to overcome a critical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-renewal, and multiple telomerase components are targeted by pluripotency-associated transcription factors.
- Suneet Agarwal
- , Yuin-Han Loh
- & George Q. Daley
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Letter |
Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET
Endogenous retroviruses (ERVs) are widely dispersed in mammalian genomes, and are silenced in somatic cells by DNA methylation. Here, an ERV silencing pathway independent of DNA methylation is shown to operate in embryonic stem cells. The pathway involves the histone H3K9 methyltransferase ESET and might be important for ERV silencing during the stages in embryogenesis when DNA methylation is reprogrammed.
- Toshiyuki Matsui
- , Danny Leung
- & Yoichi Shinkai
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Letter |
Blood stem cells emerge from aortic endothelium by a novel type of cell transition
One of two papers showing the generation of haematopoietic stem cells (HSCs) from the ventral wall of the dorsal aorta in live zebrafish embryos. Here, using imaging of live zebrafish, HSCs are shown to emerge directly from the aorta floor. This process does not involve cell division but movement of single endothelial cells out of the aorta ventral wall into the sub aortic space, where they transform into haematopoietic cells.
- Karima Kissa
- & Philippe Herbomel
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Letter |
In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium
De novo emergence of phenotypically defined haematopoietic stem cells (Sca1+, c kit+, CD41+) directly from ventral aortic haemogenic endothelial cells is shown in mice. Although the study did not visualize live embryos, it instead developed a dissection procedure to visualize the deeply located aorta.
- Jean-Charles Boisset
- , Wiggert van Cappellen
- & Catherine Robin
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Letter |
Haematopoietic stem cells derive directly from aortic endothelium during development
One of two papers showing the generation of haematopoietic stem cells (HSCs) from the ventral wall of the dorsal aorta in live zebrafish embryos. Here, combined fluorescent reporter transgenes, confocal time-lapse microscopy and flow cytometry identify and isolate the stepwise intermediates as aortic haemogenic endothelium transitions to nascent HSCs. HSCs generated from this haemogenic endothelium are the lineal founders of virtually all of the adult haematopoietic system.
- Julien Y. Bertrand
- , Neil C. Chi
- & David Traver
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Article |
Rfx6 directs islet formation and insulin production in mice and humans
Pancreatic β-cells release insulin, which controls energy homeostasis in vertebrates, and its lack causes diabetes mellitus. The transcription factor neurogenin 3 (Neurog3) initiates differentiation of β-cells and other islet cell types from pancreatic endoderm; here, the transcription factor Rfx6 is shown to direct islet cell differentiation downstream of Neurog3 in mice and humans. This may be useful in efforts to generate β-cells for patients with diabetes.
- Stuart B. Smith
- , Hui-Qi Qu
- & Michael S. German
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Letter |
Tbx3 improves the germ-line competency of induced pluripotent stem cells
The transcription factor Tbx3 is shown to significantly improve the quality of induced pluripotent stem (iPS) cells. Tbx3 binding sites in embryonic stem cells are present in genes involved in pluripotency and reprogramming factors. Furthermore, there are intrinsic qualitative differences in iPS cells generated by different methods in terms of their pluripotency, thus highlighting the need to rigorously characterize iPS cells beyond in vitro studies.
- Jianyong Han
- , Ping Yuan
- & Bing Lim
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Letter |
CHD7 cooperates with PBAF to control multipotent neural crest formation
Heterozygous mutations in the gene encoding CHD7, an ATP-dependent chromatin-remodelling protein, result in CHARGE syndrome — a disorder characterized by malformations of the craniofacial structures, peripheral nervous system, ears, eyes and heart. In humans and Xenopus, CHD7 is now shown to be essential for the formation of multipotent migratory neural crest and for activating the transcriptional circuitry of the neural crest; shedding light on the pathoembryology of CHARGE syndrome.
- Ruchi Bajpai
- , Denise A. Chen
- & Joanna Wysocka
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News |
Britain grants patent for iPS cells
The first issued outside Japan for reprogrammable stem cells credits different inventors.
- Sabin Russell
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Research Highlights |
Regenerative biology: New nerve cells connect
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Article |
Systemic signals regulate ageing and rejuvenation of blood stem cell niches
Age-associated changes in stem cell supportive niche cells are shown to deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment.
- Shane R. Mayack
- , Jennifer L. Shadrach
- & Amy J. Wagers
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Article |
Direct conversion of fibroblasts to functional neurons by defined factors
Mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. Here, mature differentiated cells are directed, via a combination of a few transcription factors (distinct from those described for generating iPS cells), to form functional neurons in vitro, without having to revert the fibroblasts to an embryonic state.
- Thomas Vierbuchen
- , Austin Ostermeier
- & Marius Wernig
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Letter |
Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency
The extent of epigenetic reprogramming in mammalian primordial germ cells (PGCs) and in early embryos, and its molecular mechanisms, are poorly understood. DNA methylation profiling in PGCs now reveals a genome–wide erasure of methylation, with female PGCs being less methylated than male ones. A deficiency of the cytidine deaminase AID interferes with the genome–wide erasure of DNA methylation, indicating that AID has a critical function in epigenetic reprogramming.
- Christian Popp
- , Wendy Dean
- & Wolf Reik
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News |
Health benefits of red-wine chemical unclear
Sceptics continue to ask whether resveratrol really can delay the effects of ageing.
- Lizzie Buchen
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Letter |
DNMT1 maintains progenitor function in self-renewing somatic tissue
Progenitor cells sustain the capacity of self-renewing tissues for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation is one potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through cell divisions. The DNA methyltransferase 1 and other regulators of DNA methylation are now shown to be essential for epidermal progenitor cell function.
- George L. Sen
- , Jason A. Reuter
- & Paul A. Khavari
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Research Highlights |
Molecular biology: Flowering time unravelled
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Letter |
Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate
Immune homeostasis relies on tight control over the size of a population of regulatory T cells (Treg) that can suppress over-exuberant immune responses. Cells commit to the Treg lineage by upregulating the transcription factor Foxp3. Conserved non-coding DNA sequence elements at the Foxp3 locus are now shown to control the composition, size and maintenance of the Treg cell population.
- Ye Zheng
- , Steven Josefowicz
- & Alexander Y. Rudensky
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Article |
Opposing microRNA families regulate self-renewal in mouse embryonic stem cells
The differentiation of an embryonic stem cell (ESC) requires both suppression of the self-renewal process and activation of the specific differentiation pathway. The let-7 family of microRNAs (miRNAs) are now shown to suppress the self-renewal program in cells that are normally unable to silence this program, whereas introduction of ESC cell cycle regulating miRNAs blocks the action of let-7. Thus, the interplay between these two groups of miRNAs dictates cell fate.
- Collin Melton
- , Robert L. Judson
- & Robert Blelloch
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