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- Parent Category: Chemistry
- Category: Medicinal
by Clive Svendsen
Results of unregulated stem cell transplant were predictable and avoidable
(This commentary provides an expert perspective to an article published in PLoS Medicine, which has been reported in Nature and Nature Reports Stem Cells.)
The study by Amariglio et al. describes a stem cell transplant attempt in a child with ataxia telangiectasia, a rare genetic disease that leads to poor coordination and dilation of blood vessels1. These patients also have weakened immune systems and are more prone to cancer.
Read more: Stem Cell Clinical Trials Must be Closely Monitored
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- Parent Category: Chemistry
- Category: Organic
by Simone Alves
MLL1 epigenetically regulates postnatal neural specification
New neurons arise in the brain throughout adulthood, but the mechanisms that maintain neurogenesis are poorly understood. By inducing a mutation that decreases the production of neurons in the young adult brain, researchers have recently established an essential role in neurogenesis for the gene-regulating enzyme known as methyltransferase MLL1.
MLL1 is one of a family of chromatin-remodelling factors — that is, proteins that control whether cells' gene-reading machinery can physically access DNA. Researchers led by Arturo Alvarez-Buylla of the University of California, San Francisco, created transgenic mice in which the Mll1 gene is deleted in neural stem cells at specific time in development1. In addition to dramatically lowering post-natal neurogenesis, the absence of Mll1 also prevented normal migration of neuronal precursors causing immature cell types to accumulate in a region known as the subventricular zone.
Read more: Chromatin Remodelling is Required For Postnatal Neurogenesis
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by Monya Baker
An analysis of when and where pluripotency factors bind indicate that c-Myc shuts down specialization and the remaining three turn on pluripotency
Scientists are still shocked that only a handful of introduced genes can turn a specialized cell's clock back so far that it behaves like an embryonic stem cell. Even with current established techniques, such reprogramming is a rare event, and researchers around the world are trying to figure out exactly how reprogramming can be triggered by genes for the pluripotency factors, which encode the transcription factors Oct4, Sox2, Klf4 and c-Myc. Publishing in Cell, researchers led by Kathrin Plath of the University of California, Los Angeles, show which genes are bound by the transcription factors in mouse embryonic stem cells, fully reprogrammed cells (induced pluripotent stem cells) and partially reprogrammed cells. The results, she believes, will help researchers find small molecules to replace the viral vectors currently used in the reprogramming process, which could result in more homogenous cells that are better suited for clinical applications.
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- Category: Organic
by Monya Baker
In the quest to switch one cell type to another, how far can tweaking transcription factors go? Thomas Graf, of the Centre for Genomic Regulation in Barcelona, is known for his work on converting one blood cell type to another. Monya Baker spoke to him about how this can be done — and why. How do you turn one cell type into another?
It's a matter of learning the changes in transcription factor networks that are instrumental in dictating cell fate. As cells develop away from each other, the transcription factor networks are more and more different, and we have to do more and more to turn one into the other.
Read more: Thomas Graf: Cellular Identity and Transdifferentiation
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- Category: Medicinal
by Monya Baker
G9a silences gene expression two ways
As embryonic stem cells differentiate, the pluripotency gene known as Oct4 goes on lockdown. In fact, the gates to gene expression are doublelocked: the gene-encoding DNA strands are wound up into a structure called heterochromatin, in which the DNA is complexed with histones and other proteins in such a way that it is inaccessible to the transcriptional machinery. Furthermore, gene-expression machinery is kept at bay by chemical modifications to the DNA that signals the start of a gene. New work published in Nature Structural and Molecular Biology1 shows not only that both of these modifications are regulated by a single master protein, the histone methyltransferase G9a, but that this enzyme apparently brings about the inactivation of many early embryonic genes.
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- Parent Category: Chemistry
- Category: Medicinal
by Monya Baker
Making blood stem cell niches in vivo and in vitro
Two independent groups of researchers have made artificial versions of the stem cell niches where blood forms. Irving Weissman and colleagues at Stanford University in California found that with the right population of cells, bone can be made to grow in the kidney. What's more, that bone can recruit a vasculature and establish a blood-forming niche, complete with haematopoietic stem cells. This marks the first in vivo assay to assess the formation and maintenance of a blood-forming niche at a site outside its natural location, and the researchers were able to use the assay to assess the ability of various soluble proteins to help establish the niche1.