LungMap Phase II - Building a multidimensional map of developing human lung

LungMap 第二阶段 - 构建人类肺部发育的多维图

基本信息

批准号：
10672949
负责人：
Jeffrey A Whitsett
金额：
$ 89.73万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-23 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10672949
关键词：
3-Dimensional ATAC-seq Acinus organ component Affect Agreement Algorithms Alveolar Alveolus Anatomy Atlases Bioinformatics Carbon Dioxide Cell Separation Cell model Cells Child Chromatin Code Collaborations Communities Complex Confocal Microscopy Congenital Disorders DNA Data Data Analyses Data Coordinating Center Data Display Defect Development Digestion Dimensions Disease Distal Doctor of Medicine Endothelium Epigenetic Process Fibroblasts Gases Gene Expression Generations Genetic Diseases Genetic Transcription Genomics Gland Goals Human Image Image Analysis Immune Immunofluorescence Immunologic In Situ In Situ Hybridization Individual Infant Intuition Link Lobule Location Lung Lung diseases Maps Mediating Molecular Morphogenesis Mus Normal tissue morphology Nuclear Nuclear RNA Online Systems Ontology Organ Oxygen Pathogenesis Patients Perinatal Phase Physiological Positioning Attribute Premature Infant Process Protein Isoforms Proteins Proteomics RNA RNA Probes RNA Splicing RNA analysis Regional Anatomy Research Resolution Role Science Signal Transduction Site Structure Structure of parenchyma of lung Submucosa Technology Tissue Procurements Tissues Trachea Visualization Work analysis pipeline analytical tool bioinformatics pipeline cell type central database confocal imaging data access data integration data visualization design diverse data droplet sequencing epigenomics experience genetic signature high resolution imaging high throughput technology human data human tissue image processing indexing insight lipidomics lung acinus structure lung development lung imaging member multidimensional data multiple omics new technology organ growth postnatal preservation programs pulmonary function reconstruction scaffold single nucleus RNA-sequencing tool transcriptome sequencing transcriptomics user-friendly web portal web services web site web-based tool

项目摘要

ABSTRACT Building a Multidimensional Map of Developing Human Lung – Jeffrey A. Whitsett, M.D. PI Our LungMAP2 project seeks to work in a collaborative consortium to develop operational pipelines to study human lung development from the saccular, alveolar stages of morphogenesis at single cell level of resolution. The project will integrate single cell transcriptomic, chromatin accessibility, 2D and 3D high-resolution confocal microscopy, immunofluorescence, multiprobe RNA in situ hybridization studies to create a detailed molecular map of the cells, cell-cell and cell scaffold interactions in their precise anatomic positions in the developing human lung. Our LungMAP2 Center will work in close concert with the Data Coordinating Center (DCC), other LungMAP2 Centers and the Human Tissue Procurement Core (HTPC) to obtain, annotate, preserve and store human tissues using optimal conditions for imaging and omics analyses. Our LungMAP2 project will produce a detailed structural expression atlas of multiple regions, niches in the human lung. We will develop and validate new technologies for tissue clearing, 3D reconstructions of high-resolution images, multi-probe RNA and IF analysis. We will develop new tissue digestion single cell and single nuclear RNA analyses for precise regional niches of the normal developing human lung, tissue from and in infants with rare congenital lung disorders. We will work in a Consortium to develop useful bioinformatic programs, modeling cell-cell, cell matrix interactions to define the signaling and transcriptional programs building and maintaining organ structure and function. Working with the DCC and other LungMAP2 Centers, our bioinformatics pipelines will enable data visualization, interrogation in user friendly web portals for sharing with members of the LungMAP2 Consortium, the DCC and for the research community in general.

抽象的构建人类肺发育的多维图 – Jeffrey A. Whitsett，医学博士 PI 我们的 LungMAP2 项目寻求与合作联盟合作，开发可操作的管道在单细胞水平上从形态发生的囊状、肺泡阶段研究人类肺的发育该项目将整合单细胞转录组、染色质可及性、2D 和 3D。高分辨率共聚焦显微镜、免疫荧光、多探针 RNA 原位杂交研究创建细胞、细胞与细胞和细胞支架相互作用的详细分子图谱我们的 LungMAP2 中心将与人类发育中的肺部的解剖位置密切合作。数据协调中心 (DCC)、其他 LungMAP2 中心和人体组织采购核心（HTPC）使用最佳条件获取、注释、保存和储存人体组织我们的 LungMAP2 项目将生成详细的结构表达图谱。我们将开发和验证人体肺部的多个区域、生态位的新技术。我们将进行透明化、高分辨率图像的 3D 重建、多探针 RNA 和 IF 分析。开发新的组织消化单细胞和单核 RNA 分析，以实现精确的区域生态位发育中的正常人肺，来自患有罕见先天性肺病的婴儿的组织。我们将在一个联盟中开发有用的生物信息学程序，对细胞-细胞、细胞基质进行建模相互作用来定义构建和维持器官的信号传导和转录程序与 DCC 和其他 LungMAP2 中心合作，我们的生物信息学。管道将实现数据可视化，在用户友好的门户网站中进行询问，以便与 LungMAP2 联盟、DCC 和整个研究界的成员。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A novel non-recurrent CNV deletion involving TBX4 and leaving TBX2 intact causes congenital alveolar dysplasia.

一种涉及 TBX4 且保留 TBX2 完整的新型非复发性 CNV 缺失会导致先天性肺泡发育不良。

DOI：
发表时间：
2024-02
期刊：
影响因子：
3.5
作者：
Bzdęga, Katarzyna;Biela, Mateusz;Deutsch, Gail H;Kitzmiller, Joseph A;Rydzanicz, Małgorzata;Płoski, Rafał;Whitsett, Jeffrey A;Śmigiel, Robert;Karolak, Justyna A
通讯作者：
Karolak, Justyna A

YAP regulates alveolar epithelial cell differentiation and AGER via NFIB/KLF5/NKX2-1.

YAP 通过 NFIB/KLF5/NKX2-1 调节肺泡上皮细胞分化和 AGER。

DOI：
发表时间：
2021-09-24
期刊：
影响因子：
5.8
作者：
Gokey, Jason J;Snowball, John;Sridharan, Anusha;Sudha, Parvathi;Kitzmiller, Joseph A;Xu, Yan;Whitsett, Jeffrey A
通讯作者：
Whitsett, Jeffrey A