Person:

Yin, Hong

Background: C/EBPα is a transcription factor essential for terminal differentiation of several cell types. It has not known if C/EBPα protein is expressed and functions in the prostate gland. Methods: The presence of C/EBPα in normal and cancerous prostate epithelium was examined by immunochemistry. Over expression of C/EBPα in LNCaP cells was conducted with retrovirus-mediated transduction. PSA expression was examined by RT-PCR and western blot and PSA promoter activity by luciferase reporter assay. Results: In normal prostate C/EBPα was expressed in the basal layer of the epithelium. In prostate cancer C/EBPα was detected at low levels throughout the cancers and in advanced prostate cancer C/EBPα expression was associated with decreased expression of AR and PSA. Overexpression of C/EBPα inhibited epigenetically PSA expression and was accompanied by the loss of expression of AR. Transient increase of C/EBPα inhibited the PSA promoter/enhancer activity independently of expression of AR. Conclusion: In LNCaP cells C/EBPα over expression inhibits expression of PSA by AR -dependent and independent mechanisms and by extinguishing AR expression provides a model for hormonal independent cell growth.

Platelets play an essential role in hemostasis and atherothrombosis. Owing to their short storage time, there is constant demand for this life-saving blood component. In this study, we report that it is feasible to generate functional megakaryocytes and platelets from human embryonic stem cells (hESCs) on a large scale. Differential-interference contrast and electron microscopy analyses showed that ultrastructural and morphological features of hESC-derived platelets were indistinguishable from those of normal blood platelets. In functional assays, hESC-derived platelets responded to thrombin stimulation, formed microaggregates, and facilitated clot formation/retraction in vitro. Live cell microscopy demonstrated that hESC-platelets formed lamellipodia and filopodia in response to thrombin activation, and tethered to each other as observed in normal blood. Using real-time intravital imaging with high-speed video microscopy, we have also shown that hESC-derived platelets contribute to developing thrombi at sites of laser-induced vascular injury in mice, providing the first evidence for in vivo functionality of hESC-derived platelets. These results represent an important step toward generating an unlimited supply of platelets for transfusion. Since platelets contain no genetic material, they are ideal candidates for early clinical translation involving human pluripotent stem cells.

Social anhedonia (SA) is a debilitating characteristic of schizophrenia, a common feature in individuals at psychosis-risk, and a vulnerability for developing schizophrenia-spectrum disorders. Prior work (Hooker et al., 2014) revealed neural deficits in the ventral lateral prefrontal cortex (VLPFC) when processing positive social cues in a community sample of people with high SA. Lower VLPFC neural activity was related to more severe self-reported schizophrenia-spectrum symptoms as well as the exacerbation of symptoms after social stress. In the current study, psycho-physiological interaction (PPI) analysis was applied to further investigate the neural mechanisms mediated by the VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA exhibited reduced connectivity between the VLPFC and the motor cortex, the inferior parietal and the posterior temporal regions when viewing socially positive (relative to neutral) emotions. Across all participants, VLPFC connectivity correlated with behavioral and self-reported measures of attentional control, emotion management, and reward processing. Our results suggest that impairments to the VLPFC mediated neural circuitry underlie the cognitive and emotional deficits associated with social anhedonia, and may serve as neural targets for prevention and treatment of schizophrenia-spectrum disorders.