Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues

Molecular mechanisms of organismal and cell aging remain incompletely understood. We, therefore, generated a body-wide map of noncoding RNA (ncRNA) expression in aging (16 organs at ten timepoints from 1 to 27 months) and rejuvenated mice. We found molecular aging trajectories are largely tissue-specifc except for eight broadly deregulated microRNAs (miRNAs). Their individual abundance mirrors their presence in circulating plasma and extracellular vesicles (EVs) whereas tissue-specifc ncRNAs were less present. For miR-29c-3p, we observe the largest correlation with aging in solid organs, plasma and EVs. In mice rejuvenated by heterochronic parabiosis, miR-29c-3p was the most prominent miRNA restored to similar levels found in young liver. miR-29c-3p targets the extracellular matrix and secretion pathways, known to be implicated in aging. We provide a map of organism-wide expression of ncRNAs with aging and rejuvenation and identify a set of broadly deregulated miRNAs, which may function as systemic regulators of aging via plasma and EVs

The Human Cell Atlas White Paper

The Human Cell Atlas (HCA) will be made up of comprehensive reference maps of all human cells - the fundamental units of life - as a basis for understanding fundamental human biological processes and diagnosing, monitoring, and treating disease. It will help scientists understand how genetic variants impact disease risk, define drug toxicities, discover better therapies, and advance regenerative medicine. A resource of such ambition and scale should be built in stages, increasing in size, breadth, and resolution as technologies develop and understanding deepens. We will therefore pursue Phase 1 as a suite of flagship projects in key tissues, systems, and organs. We will bring together experts in biology, medicine, genomics, technology development and computation (including data analysis, software engineering, and visualization). We will also need standardized experimental and computational methods that will allow us to compare diverse cell and tissue types - and samples across human communities - in consistent ways, ensuring that the resulting resource is truly global. This document, the first version of the HCA White Paper, was written by experts in the field with feedback and suggestions from the HCA community, gathered during recent international meetings. The White Paper, released at the close of this yearlong planning process, will be a living document that evolves as the HCA community provides additional feedback, as technological and computational advances are made, and as lessons are learned during the construction of the atlas

Pilot study demonstrating changes in DNA hydroxymethylation enable detection of multiple cancers in plasma cell-free DNA

ABSTRACTOur study employed the detection of 5-hydroxymethyl cytosine (5hmC) profiles on cell free DNA (cfDNA) from the plasma of cancer patients using a novel enrichment technology coupled with sequencing and machine learning based classification method. These classification methods were develoiped to detect the presence of disease in the plasma of cancer and control subjects. Cancer and control patient cfDNA cohorts were accrued from multiple sites consisting of 48 breast, 55 lung, 32 prostate and 53 pancreatic cancer subjects. In addition, a control cohort of 180 subjects (non-cancer) was employed to match cancer patient demographics (age, sex and smoking status) in a case-control study design.Logistic regression methods applied to each cancer case cohort individually, with a balancing non-cancer cohort, were able to classify cancer and control samples with measurably high performance. Measures of predictive performance by using 5-fold cross validation coupled with out-of-fold area under the curve (AUC) measures were established for breast, lung, pancreatic and prostate cancer to be 0.89, 0.84, 0.95 and 0.83 respectively. The genes defining each of these predictive models were enriched for pathways relevant to disease specific etiology, notably in the control of gene regulation in these same pathways. The breast cancer cohort consisted primarily of stage I and II patients, including tumors &lt; 2 cm and these samples exhibited a high cancer probability score. This suggests that the 5hmC derived classification methodology may yield epigenomic detection of early stage disease in plasma. Same observation was made for the pancreatic dataset where &gt;50% of cancers were stage I and II and showed the highest cancer probability score.</jats:p

Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during a period of rapid postnatal growth

SummaryAt birth, the lung is still immature, heightening susceptibility to injury but enhancing regenerative capacity. Angiogenesis drives postnatal lung development. Therefore, we profiled the transcriptional ontogeny and sensitivity to injury of pulmonary endothelial cells (EC) during early postnatal life. Although subtype speciation was evident at birth, immature lung EC exhibited transcriptomes distinct from mature counterparts, which progressed dynamically over time. Gradual, temporal changes in aerocyte capillary EC (CAP2), contrasted with more marked alterations in general capillary EC (CAP1) phenotype, including distinct CAP1 present only in the early alveolar lung expressingPeg3, a paternally imprinted transcription factor. Hyperoxia, an injury which impairs angiogenesis, induced both common and unique endothelial gene signatures, dysregulated capillary EC cross-talk, and suppressed CAP1 proliferation while stimulating venous EC proliferation. These data highlight the diversity, transcriptomic evolution, and pleiotropic responses to injury of immature lung EC, possessing broad implications for lung development and injury across the lifespan.</jats:p

Applying single-cell and single-nucleus genomics to studies of cellular heterogeneity and cell fate transitions in the nervous system

Single-cell and single-nucleus genomic approaches can provide unbiased and multimodal insights. Here, we discuss what constitutes a molecular cell atlas and how to leverage single-cell omics data to generate hypotheses and gain insights into cell transitions in development and disease of the nervous system. We share points of reflection on what to consider during study design and implementation as well as limitations and pitfalls.UPLAMANN

Juicy Game Design: Understanding the Impact of Visual Embellishments on Player Experience

Visual embellishments (VEs) are design elements that support information already conveyed by other means. In games, this concept is known as juiciness, and refers to the provision of redundant feedback in situations where a single player action triggers multiple non-functional reactions. Academia and industry both view the concept as a means of improving player experience; however, empirical evidence to back the assumption is lacking. Here, we present findings from two studies: one initial study with 40 participants comparing the effects of visual embellishments in two research games, the Frogger-clone Cuber, and the FPS game Dungeon Descent, and a second study with 32 participants using the commercially available game Quake 3 Arena. Results show that visual embellishments contribute to the visual appeal of all games, but only affects aspects such as competence under specific circumstances. We discuss implications of our findings for the integration of visual embellishments and juiciness, and their relevance for game development

The Human Cell Atlas

AbstractThe recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body, by undertaking a Human Cell Atlas Project as an international collaborative effort. The aim would be to define all human cell types in terms of distinctive molecular profiles (e.g., gene expression) and connect this information with classical cellular descriptions (e.g., location and morphology). A comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, as well as provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas.</jats:p