Multiscale, Multimodal Analysis of Skin and Spatial Cell Organization

项目摘要/摘要(总体) 我们对皮肤组织映射中心(TMC)的愿景是创建首创的、全面的、2D和3D的 正常皮肤的空间分辨多组体空间图谱，包括细胞类型、脂质组学和 转录学。样本将前瞻性地从四个主要的身体部位收集，包括头部和 颈部、背部、腹部和四肢连续的肤色(使用更客观的Fitzpatrick 比例)。许多关于皮肤细胞类型的原始研究现在已经有几十年的历史了，并使用 单链IHC或批量基因组分析。尽管有皮肤地图集，但它们更关注疾病，以及 往往缺乏肤色的多样性和变化性。皮肤老化是一个动态过程，在这个过程中 在理解它是如何随着肤色和紫外线暴露而变化的方面进展甚微。这部小说 跨越肤色和位置的皮肤细胞类型的空间参考图将提供关键的新见解 健康的皮肤特征。预期的样本收集提供了定制构建 包含更多可能影响皮肤健康的临床信息的数据库。虽然我们将重点放在 招募种族多元化的人群，患者将标准化为6分菲茨帕特里克皮肤 色度表，最初是为了评估光疗中紫外线损伤的风险而开发的。使用这个标尺 使我们能够采取更客观的方法来评估皮肤健康的差异以及紫外线和衰老的影响。 该项目将由GE Research与匹兹堡大学(PITT)-部门合作领导 皮肤科。皮特-皮肤科可以接触到大量的患者和志愿者 不同的背景，每年处理大约2万个皮肤样本。我们将利用这些人口 从不同的解剖部位(头、颈、背部、 腹部和四肢)。来自年轻和老年年龄组的捐赠者的样本以及来自 不同的肤色，如Fitzpatrick Scale I-VI所记录的，将被前瞻性地收集。通用电气研究公司将 负责空间单细胞分析，并将脂质组学和空间转录组学整合为 多模式的2D和3D皮肤图集。

PROJECT SUMMARY/ABSTRACT (OVERALL) Our vision for the Skin Tissue Mapping Center (TMC) is to create a first-of-its-kind, comprehensive, 2D and 3D spatially-resolved multi-omic spatial atlas of normal skin comprising cell types, lipidomics, and transcriptomics. Samples will be prospectively collected from four major body locations including head and neck, back, abdomen and extremities across the continuum of skin colors (using the more objective Fitzpatrick scale). Many of the original studies on skin cell types are now several decades old and conducted using singleplex IHC or bulk genomic analysis. Although skin atlases exist, they are more focused on disease, and tend to be lacking in diversity and variation of skin tones. Skin aging is a dynamic process in which there has been little advancement in understanding how it varies as a function of skin tone and UV exposure. This novel spatial reference map of skin cell types spanning skin tone and location will provide critical new insights into healthy skin characteristics. Prospective sample collection provides the unique opportunity to custom build a database with more extensive clinical information that may affect skin health. Although we will focus on recruitment of an ethnically diverse population, patients will be standardized to the 6-point Fitzpatrick skin color scale, which was originally developed to assess risk of UV damage from phototherapy. Using this scale allows us to take a more objective approach to assessing differences in skin health and effects of UV and aging. This program will be led by GE Research in collaboration with the University of Pittsburgh (Pitt)-Department of Dermatology. Pitt-Department of Dermatology has access to a large patient and volunteer population with diverse backgrounds, with about 20,000 skin specimens processed every year. We will leverage this population to collect up to 96 well-curated samples from various anatomically-distinct skin locations (head and neck, back, abdomen and extremities). Samples from donors across younger and elderly age groups and from persons of diverse skin colors, as recorded by Fitzpatrick scale types I-VI, will be prospectively collected. GE Research will be responsible for spatial single-cell analysis and integration of lipidomics and spatial transcriptomics into a multi-modal 2D and 3D atlas of skin.