Person:

Liu, Rui

Long non-coding RNAs (lncRNAs) regulate diverse biological processes, including cell lineage specification. Here, we report transcriptome profiling of human endoderm and pancreatic cell lineages using purified cell populations. Analysis of the data sets allows us to identify hundreds of lncRNAs that exhibit differentiation-stage-specific expression patterns. As a first step in characterizing these lncRNAs, we focus on an endoderm-specific lncRNA, definitive endoderm-associated lncRNA1 (DEANR1), and demonstrate that it plays an important role in human endoderm differentiation. DEANR1 contributes to endoderm differentiation by positively regulating expression of the endoderm factor FOXA2. Importantly, overexpression of FOXA2 is able to rescue endoderm differentiation defects caused by DEANR1 depletion. Mechanistically, DEANR1 facilitates FOXA2 activation by facilitating SMAD2/3 recruitment to the FOXA2 promoter. Thus, our study not only reveals a large set of differentiation-stage-specific lncRNAs but also characterizes a functional lncRNA that is important for endoderm differentiation.

Purpose Peripheral prisms (p-prisms) shift peripheral portions of the visual field of one eye, providing visual field expansion for patients with hemianopia. However, patients rarely show adaption to the shift, incorrectly localizing objects viewed within the p-prisms. A pilot evaluation of a novel computerized perceptual-motor training program aiming to promote p-prism adaption was conducted. Methods: Thirteen patients with hemianopia fitted with 57Δ oblique p-prisms completed the training protocol. They attended six 1-hour visits reaching and touching peripheral checkerboard stimuli presented over videos of driving scenes while fixating a central target. Performance was measured at each visit and after 3 months. Results: There was a significant reduction in touch error (P = 0.01) for p-prism zone stimuli from pretraining median of 16.6° (IQR 12.1°–19.6°) to 2.7° ( IQR 1.0°–8.5°) at the end of training. P-prism zone reaction times did not change significantly with training (P > 0.05). P-prism zone detection improved significantly (P = 0.01) from a pretraining median 70% (IQR 50%–88%) to 95% at the end of training (IQR 73%–98%). Three months after training improvements had regressed but performance was still better than pretraining. Conclusions: Improved pointing accuracy for stimuli detected in prism-expanded vision of patients with hemianopia wearing 57Δ oblique p-prisms is possible and training appears to further improve detection. Translational Relevance This is the first use of this novel software to train adaptation of visual direction in patients with hemianopia wearing peripheral prisms.