Homologue of Enhancer-of-split 1 (Hes1) is a transcription factor that regulates neuronal plasticity, promoting the growth of dendrites and increasing the GABAergic input. A higher expression of Hes1 also results in neuronal resistance against the noxious activity of amyloid beta, the main agent in the advent and progression of the Alzheimer's disease. As a transcription factor, Hes1 controls de expression of many genes. Using the microarray technology we have detected that the expression of one secreted synaptic protein, cerebellin 4 (Cbln4) was particularly increased upon overexpression of Hes1. We also present evidence that Cbln4 plays an essential role in the formation and maintenance of inhibitory GABAergic connections and that either overexpression of Cbln4 in cultured hippocampal neurons or the application of recombinant Cbln4 to the cultures increased the number of GABAergic varicosities and rescued neurons from amyloid beta induced cell death.
Cerebellin 4, a synaptic protein, enhances inhibitory activity and resistance of neurons to amyloid-β toxicity.
Specimen part
View SamplesMolecular mechanisms that are responsible for the development of human skin epithelial cells are not completely understood so far. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSC) remains poor. Using an approach including RNA interference and high-throughput imaging of early epithelial cells, we could identify candidate kinases which are involved in skin epithelial differentiation. Among them, we found HIPK4 to be an important inhibitor of this process. Indeed, its silencing increased the amount of generated skin epithelial precursors, increased the amount of generated keratinocytes and improved growth and differentiation of organotypic cultures, allowing for the formation of a denser basal layer and stratification with the expression of several keratins. Our data bring substantial input in the regulation of human skin epithelial differentiation and for improving differentiation protocols from pluripotent stem cells.
An RNAi Screen Reveals an Essential Role for HIPK4 in Human Skin Epithelial Differentiation from iPSCs.
Specimen part, Time
View SamplesWe report two clusters in the overall profiles of expression among the samples. At the parasitemia onset, there is a strong interferon response reflected in up-regulation of co-regulated transcripts, while unexpectedly we also see down-regulation of transcripts related to TLR signaling and innate immunity. RNASeq also suggested differential expression of reticulocytes and a subset of T cell function. No obvious difference in the transcriptomes of naïve and semi-immune volunteers was seen, however several hundred genes were up-regulated in naïve individuals. Overall design: RNA-seq analysis was performed for 12 individuals (6 each from Buenaventura and Cali) for two of the time points, namely the diagnosis day and baseline (pre-challenge day).
Integrative metabolomics and transcriptomics signatures of clinical tolerance to Plasmodium vivax reveal activation of innate cell immunity and T cell signaling.
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