Developing in situ transcriptomics of a bioprinted follicular skin model

开发生物打印毛囊皮肤模型的原位转录组学

基本信息

批准号：
10678027
负责人：
Julia S Oh
金额：
$ 43.88万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2025-09-14
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10678027
关键词：
3-Dimensional Address Admixture Bacteria Bar Codes Biodiversity Biology Cell Communication Cells Chromosome Mapping Collagen Complex Confocal Microscopy Coupled Cutaneous Data Dermal Development Disease Ecosystem Epidermis Epithelial Cells Epithelium Fibroblasts Functional disorder Gene Expression Profiling Genes Genetic Transcription Gland Goals Hair follicle structure Health High-Throughput Nucleotide Sequencing Histology Homeostasis Human Immune system Immunity Immunohistochemistry In Situ In Vitro Infection Infectious Skin Diseases Inflammatory Investigation Knowledge Libraries Maps Metagenomics Methods Microbe Modeling Molecular Mus Nature Operative Surgical Procedures Physiological Play Population Predisposition Public Health Regulation Research Personnel Resolution Role Sebaceous Glands Skin Skin Cancer Skin Tissue Spatial Distribution Stimulus Stratum corneum Structure Techniques Technology The Jackson Laboratory Therapeutic Tissue Model Tissues Transcript Variant Virulence Virus Visualization Work aspirate base bioprinting cell type empowerment experimental study fabrication fungus host microbiome host-microbe interactions human model in situ sequencing in vitro Model keratinocyte microbial microbial colonization microbiome microorganism interaction multidisciplinary new technology pathobiont response skin barrier skin disorder skin microbiome spatial relationship success therapeutic target tissue culture tongue papilla transcriptomics

项目摘要

PROJECT SUMMARY / ABSTRACT The goal of this proposal is to develop a platform to model host-microbe interactions in skin, featuring a 3D bioprinted follicular skin model and spatial transcriptomics of host and microbial cells to retain physiologically relevant interactions. In human skin, a majority of microbial interactions with the host epithelium and cutaneous immunity is thought to occur in deeper, protective adnexal structures, e.g., hair follicles and glands. For example, recent work in mice has suggested a homeostatic interaction between different tissue resident cells, sebaceous glands, and the microbiome. Given the substantial diversity of the microbiome – encompassing hundreds of different bacterial and fungal species, it would be highly impactful to model such potential interactions systematically. In addition, examining interactions with human cells would best provide translational data on cellular response to microbial colonization. However, there are major limitations in the 3D skin models that are available – they lack complex structures where skin microbes reside, and second, current approaches to investigate host-microbiome interactions lack resolution on spatial activity. Here, our two aims address these key limitations. In Aim 1, we will develop a 3D bioprinted skin tissue model containing follicular structures. In Aim 2, we will develop in situ microbial sequencing technology for spatial profiling of microbial colonization of these tissues and other available human 3D skin models. These aims taken together will allow us to address fundamental questions on the underlying biology of the skin microbiome, which we will pilot in this R21. Our success would result in two new technologies that would enable construction of a high-resolution spatial map of the microbiome and host interactions, enabling foundational investigations into mechanisms of interstrain interactions and regulation of virulence to promote skin homeostasis.

项目摘要 /摘要该提案的目的是开发一个平台，以模拟皮肤中的宿主微型互动，以3D为特征宿主和微生物细胞的生物打印的follic皮肤模型和空间转录组学以保持物理保留相关互动。在人皮肤中，大多数微生物与宿主上皮和皮肤的相互作用免疫被认为发生在更深的，受保护的附件结构中，例如毛囊和腺体。为了例如，在小鼠中最近的工作表明，不同组织居民细胞之间的稳态相互作用，皮脂利亚舞和微生物组。考虑到微生物组的实质性多样性 - 包含数百种不同的细菌和真菌物种，对这种潜力进行建模将具有很大的影响系统上的交互。此外，检查与人类细胞的相互作用最好提供关于微生物定植的细胞反应的翻译数据。但是，3D有主要限制可用的皮肤模型 - 它们缺乏皮肤微生物居住的复杂结构，其次是当前的研究宿主 - 微生物组相互作用的方法缺乏对空间活性的分辨率。在这里，我们的两个目标解决这些关键限制。在AIM 1中，我们将开发一个3D生物打印的皮肤组织模型，其中包含滤泡结构。在AIM 2中，我们将开发原位微生物测序技术，用于微生物的空间分析这些组织和其他可用的人类3D皮肤模型的定殖。这些目标将允许我们要解决有关皮肤微生物组的基本生物学的基本问题，我们将试行这个R21。我们的成功将导致两种新技术，这些技术可以建设高分辨率微生物组和宿主相互作用的空间图，从而实现了对机制的基础研究交流间相互作用和病毒的调节以促进皮肤稳态。