Citations

Abstract Spatial transcriptomics has been widely applied to study the spatial distribution of cell types, cell states, and specific gene expression in tissue samples. However, we show that there is a prevalent transcript leakage problem in spatial transcriptomics data, where transcripts expressed by a cell diffuse to its neighborhood and are recurrently detected in the nearby cells. By analyzing published data sets, we show that this problem is general across data produced from different tissues and different species using different imaging-based and sequencing-based spatial transcriptomics platforms. It affects both upstream tasks such as expression quantification as well as downstream tasks such as cell-type annotation and detection of spatially-dependent gene expression. To tackle the transcript leakage problem, we propose a reference-free Bayesian model-based method, DeLeakage, which cleans up the data much more effectively than existing denoising methods. DeLeakage also improves cell-type annotation and avoids false detection of spatially dependent expression.

ABSTRACT Evidence indicates that the integrity of in utero development influences late life healthy or unhealthy aging; however, specific links between them are unclear. Histone chaperone HIRA is thought to play a role in both life stages, and here, we explore this role using the murine pigmentary system by investigating and comparing the effects of its lineage‐specific knockout, either conditionally during embryogenesis or postnatally. Embryonic knockout of Hira in tyrosinase+ neural crest‐derived lineages, including melanoblasts, led to reduced melanoblast numbers during embryogenesis, with single‐cell RNA sequencing analysis indicating evidence of lineage‐specificity defects. This was supported in an in vitro model using melb‐a melanoblasts in which Hira knockdown affected lineage identity and melanoblast differentiation potential, with ATAC‐seq data indicating a role of HIRA in orchestrating chromatin accessibility. Interestingly, however, newborn Hira knockout mice had wild type numbers of differentiated melanocytes, albeit functionally defective, as demonstrated by very mild hypopigmentation of the first hair coat, increased melanocyte telomere‐associated DNA damage foci, and impaired response to proliferative challenge. Moreover, as they aged, mice with embryonic melanoblast Hira knockout displayed marked defects in melanocyte stem cell maintenance and premature hair graying. Importantly, this phenotype was not observed after postnatal inducible knockout, indicating an essential role for HIRA at embryonic stages that is transmitted to adulthood, rather than a direct postnatal requirement within the pigmentary system. This genetic model shows that HIRA function during early development lays a foundation for maintaining lineage identity and subsequent maintenance of adult tissue‐specific stem cells during aging.

AbstractBackgroundTraditionally, there has been a reluctance to use weight training with female gymnasts due to concerns that it could cause detrimental increases in muscle mass and impede flexibility. Recent literature has demonstrated that strength training has no significant effect on flexibility and can improve athletic performance.ObjectiveTo assess in a pilot study the perceptions of collegiate gymnasts and coaches toward strength training after starting inaugural strength and conditioning training.DesignSurvey‐based study.SettingNational Collegiate Athletics Association Division I women's gymnastics program at a public university in California.ParticipantsOf the 23 gymnasts surveyed, 17 (74%) responded to the survey. Of the two coaches surveyed, both (100%) responded to the survey.InterventionsNot applicable.Main Outcome MeasuresDescriptive statistics characterizing demographics, characteristics of gymnasts' strength and conditioning program, and perceptions regarding the safety of strength training and its impact on performance, body shape, flexibility, and injury rates.ResultsMost gymnasts agreed (35%) or strongly agreed (59%) that weight training may improve performance. All gymnasts disagreed (59%) or strongly disagreed (41%) that weight training is not safe; 41% disagreed, 29% strongly disagreed, and 17% agreed that weight training may negatively affect body shape. Most gymnasts disagreed (59%) or strongly disagreed (18%) that weight training decreases flexibility; four (24%) felt neutral. Eighty three percent (59% strongly agree, 24% agree) felt that weight training had a positive impact on performance. More than half of the gymnasts either agreed (24%) or strongly agreed (29%) they had fewer injuries the season after implementing weight training, compared to prior seasons. Both coaches similarly endorsed the safety of strength training and its potential to improve performance.ConclusionsIn this pilot study, collegiate gymnasts and coaches expressed generally positive perceptions toward the safety of strength training and its effect on performance. A small number of gymnasts expressed concerns regarding the effects of weight training on body shape and flexibility.