Defining the human adventitial stem cell niche

定义人类外膜干细胞生态位

基本信息

批准号：
10685946
负责人：
AARON W JAMES
金额：
$ 17.76万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-18 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10685946
关键词：
Adipose tissue Antibodies Autologous Biological Assay Blood Vessels Bone Regeneration Bone Tissue CD34 gene Cell Fraction Cell Therapy Cell surface Cells Clinical Trials Collagen Defect Development Engineering Fatty acid glycerol esters Frequencies Future Geography Heterogeneity Histologic Human Knowledge Laboratories Location Mesenchymal Microanatomy Modeling Molecular Analysis Multipotent Stem Cells Mus Natural regeneration Pathologic Pericytes Population Property Regenerative Medicine Reporter Role Sampling Series Speed Stromal Cells Time Tissue Engineering Tissues Transplantation Trees Tunica Adventitia Work Xenograft procedure adipose derived stem cell bone bone repair cell preparation cell type clinical application healing improved insight interest novel osteogenic osteoprogenitor cell self-renewal single-cell RNA sequencing skeletal skeletal tissue stem stem cell niche stem cell therapy stem cells subcutaneous tissue regeneration transcriptomics

项目摘要

PROJECT SUMMARY The vascular tree is exquisitely organized into concentric layers, the outermost layer termed the tunica adventitia. The bulk of multipotent progenitor cells within fat tissue lie within the adventitia, yet the cellular diversity within this stem cell niche is only now being uncovered. Our laboratory has demonstrated a promising role for FACS purified human adventitial cells (adventicytes) to induce and participate in bone regeneration (Wang et al., NPJ Regen Med 2018). Despite a conserved adventitial location, when perivascular cells are studied with an -omics approach, a rich heterogeneity of cell types exists even among purified cell populations. In order to probe this cellular diversity, we recently employed several high throughput approaches, including single cell RNA sequencing and cell surface antibody arrays, to further define the stem cell hierarchy of CD34+ adventicytes (Xu et al., Elife 2020). Our recent findings suggest that a continuum of cell types exist within this microanatomical stem cell niche, and that novel cell surface markers highlight histologically distinct and functionally relevant adventitial subpopulations (Ding et al., Stem Cells 2020). The current exploratory proposal capitalizes on this series of observations, seeking for the first time to examine the functionally relevant cellular diversity within the adventitial niche of human adipose tissue. Our hope is that the proof-of-concept studies outlined here will provide an essential lynchpin in our future choice of perivascular progenitor cells for clinical applications in skeletal regenerative medicine.

项目概要维管树精致地组织成同心层，最外层称为被膜外膜。脂肪组织内的大部分多能祖细胞位于外膜内，但细胞这个干细胞生态位内的多样性现在才被发现。我们的实验室展示了一种有前景的 FACS 纯化的人外膜细胞 (adventicytes) 诱导和参与骨再生的作用（Wang 等人，NPJ Regen Med 2018）。尽管外膜位置保守，但当血管周围细胞通过组学方法进行研究，即使在纯化的细胞群中也存在丰富的细胞类型异质性。为了探测这种细胞多样性，我们最近采用了几种高通量方法，包括单细胞 RNA 测序和细胞表面抗体阵列，进一步定义 CD34+ 的干细胞层次结构外膜细胞（Xu 等人，Elife 2020）。我们最近的发现表明，该细胞类型中存在连续体显微解剖干细胞生态位，并且新颖的细胞表面标记突出了组织学上的独特和功能相关的外膜亚群（Ding et al., Stem Cells 2020）。目前的探索性提案利用了这一系列的观察结果，首次寻求检验人类脂肪组织外膜生态位内功能相关的细胞多样性。我们的希望是这里概述的概念验证研究将为我们未来选择血管周围药物提供重要的关键祖细胞在骨骼再生医学中的临床应用。