Project description:Analysis of gene expression profile of Tibialis anterior (TA) skeletal muscle tissues with Notch1 intracellular domain (N1ICD) overexpression. Skeletal myogenesis involves sequential activation, proliferation, self-renewal/differentiation and fusion of myogenic stem cells (satellite cells). Notch signaling is known to be essential for the maintenance of satellite cells, but its function in late-stage myogenesis, i.e. post-differentiation myocytes and post-fusion myotubes, is unknown. Here we use muscle creatine kinase (MCK)-Cre to induce N1ICD expression in multinucleated myotubes. We found that myotube-specific Notch1 activation improved muscle regeneration and exercise performance of mdx mice, a model of Duchenne Muscular Dystrophy (DMD). Agilent microarray was performed to compare gene expression in mdx control and N1ICD-overexpressing mdx muscles. The results may provide mechanistic insights into how Notch1 activation in myotubes modulate muscle function.
Project description:The Notch signaling pathway regulates several differentiation and developmental processes, and is involved in the development of a multitude of diseases. Here we investigate by ChIP-Seq the effects of overexpression of the active NOTCH1 intracellular domain (N1ICD) on H3K27ac in human adipose tissue endothelial cells.
Project description:To investigate the regulatory role of Notch1 signaling pathway in mouse prostate growth and development, we constructed mice with prostate-specific overactivation of Notch1 intracellular domain N1ICD, in which Notch1 signaling was overactivated in prostate epithelial cells. We then analyzed gene expression profiles in the prostates of overexpressed and normal Notch1 mice.
Project description:The adaptation of regimented exercise in skeletal muscle including muscular hypertrophy and enhanced strength decline significantly with aging. Transcriptome analysis following RNA sequencing reveals extensive activation of hypoxia-related genes in young exercised mice versus the sedentary, but absent in aged exercised mice. Particularly, less expression of aryl hydrocarbon receptor translocator (ARNT) was observed in response to exercise in aged mice. Young mice underwent skeletal muscle-specific knockout of ARNT (ARNT mKO) obtain deficient benefit from exercise resembling the aged mice. The deletion of ARNT associated with decreased expression of Notch1 intracellular domain(N1ICD) impair muscle hypertrophy and regeneration. Administration of ML228, a systematic agonist of ARNT, rescued skeletal muscle adaptabilities in old mice, which was suppressed by administrating N1ICD inhibitor(DAPT). These results suggest that the loss of skeletal muscle ARNT is partially responsible for diminished response to exercise in aging and activation of hypoxia signaling holds promise for rescuing the adaptability in aged muscle.
Project description:Mechanisms guiding the induction of blood-brain barrier (BBB) properties in central nervous system (CNS) endothelial cells during human development are incompletely understood. To explore induction of reduced vesicular endocytosis and transcytosis properties in a human in vitro model of the BBB, we used human pluripotent stem cell (hPSC)-derived endothelial progenitor cells (EPCs) in which Wnt/β-catenin signaling was activated to generate hPSC-derived CNS-like ECs (hPSC-CECs). We assessed the effects of Notch signaling through overexpression of the Notch1 receptor intracellular domain (N1ICD). N1ICD overexpression in hPSC-CECs was induced by treatment with doxycycline (Dox), and hPSC-CECs were sorted into subpopulations by FACS based on high or low surface expression of CD144/VE-cadherin (CD144hi or CD144lo, respectively). Several negative control replicates treated with PBS (nearly all of which were CD144hi), were included as well. Our findings indicate that Notch signaling differentially regulates vesicular endocytosis and transcytosis-related genes in a human model of the developing BBB, contributing to our understanding of how Notch signaling induces these specific BBB properties in this model of human CNS EC development.
Project description:Notch signaling is an evolutionarily conserved signaling pathway.NOTCH3 signaling has been shown to potentially paly an important role in luminal cell fate commitment in human breast tissue by regulating unique target genes We overexpressed the intracellular domain of NOTCH1 (N1ICD) and NOTCH3 (N3ICD) receptor in nonmalignant human breast cell line, 184-hTerts
Project description:Overexpression of intracellular domain(NICD) of Notch1 affected the expression level of more than 1000 genes 6 samples were analyzed
