Česká Genetická Banka

SCIENCE: 10. 5. 2013

SCIENCE: Simple Genetics for a Complex Disease

"The cost of bringing a drug to market is staggering (estimated at more than 1 billion dollars) and the failure rate is daunting: Only one in three drugs that reach phase 3 clinical trials ultimately reach the marketplace. Accordingly, there has been considerable interest in improving strategies to predict the effects of new therapeutic agents. The outcome of several recent trials of a new class of cholesterol-lowering agents—antibodies against an enzyme called proprotein convertase subtilisin kexin type 9 (PCSK9) (1) — illustrates the potential role of human genetics not only in identifying drug targets, but also in predicting the likely consequences of specific interventions."

http://www.sciencemag.org/content/340/6133/689.summary

 

NATURE: Mechanism for Alzheimer's delay

"Studies suggest that symptoms of Alzheimer's disease can be delayed if people keep their brains active, and researchers have now uncovered a potential underlying mechanism."

http://www.nature.com/nature/journal/v497/n7448/full/497161d.html

 

NATURE: M-CSF instructs myeloid lineage fate in single haematopoietic stem cells

"Under stress conditions such as infection or inflammation the body rapidly needs to generate new blood cells that are adapted to the challenge. Haematopoietic cytokines are known to increase output of specific mature cells by affecting survival, expansion and differentiation of lineage-committed progenitors^{1, 2}, but it has been debated whether long-term haematopoietic stem cells (HSCs) are susceptible to direct lineage-specifying effects of cytokines. Although genetic changes in transcription factor balance can sensitize HSCs to cytokine instruction³, the initiation of HSC commitment is generally thought to be triggered by stochastic fluctuation in cell-intrinsic regulators such as lineage-specific transcription factors^{4, 5, 6, 7}, leaving cytokines to ensure survival and proliferation of the progeny cells^{8, 9}. Here we show that macrophage colony-stimulating factor (M-CSF, also called CSF1), a myeloid cytokine released during infection and inflammation, can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change in mouse HSCs, independently of selective survival or proliferation. (...)"

http://www.nature.com/nature/journal/v497/n7448/full/nature12026.html

 

NATURE: Meis1 regulates postnatal cardiomyocyte cell cycle arrest

"The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation^{1, 2}. However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown^{3, 4}. Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. (...)"

http://www.nature.com/nature/journal/v497/n7448/full/nature12054.html

 

NATURE: Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota

"Peripheral mechanisms preventing autoimmunity and maintaining tolerance to commensal microbiota involve CD4⁺ Foxp3⁺ regulatory T (T_reg) cells^{1, 2} generated in the thymus or extrathymically by induction of naive CD4⁺ Foxp3⁻ T cells. Previous studies suggested that the T-cell receptor repertoires of thymic T_reg cells and induced T_reg cells are biased towards self and non-self antigens, respectively^{3, 4, 5, 6}, but their relative contribution in controlling immunopathology, such as colitis and other untoward inflammatory responses triggered by different types of antigens, remains unresolved⁷. (...)"

http://www.nature.com/nature/journal/v497/n7448/full/nature12079.html