Defining the human adventitial stem cell niche

项目总结 维管树被巧妙地组织成同心的层，最外层被称为膜层 外膜。脂肪组织内的大部分多能祖细胞位于外膜内，而细胞 这个干细胞利基中的多样性直到现在才被发现。我们的实验室已经证明了一种有希望的 流式细胞仪纯化的人外膜细胞诱导和参与骨再生的作用 (Wang等人，NPJ Regen Med 2018)。尽管有保守的外膜位置，但当血管周围细胞 用AN组学方法研究，即使在纯化的细胞群体中也存在丰富的细胞类型异质性。 为了探索这种细胞多样性，我们最近采用了几种高吞吐量的方法，包括 单细胞RNA测序和细胞表面抗体阵列，以进一步确定CD34+的干细胞层级 Adventicytes(Xu等人，eLife 2020)。我们最近的发现表明，在这一过程中存在一系列细胞类型 显微解剖干细胞利基，以及新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等人，干细胞2020)。 目前的探索性提案利用了这一系列观察，首次寻求检查 人类脂肪组织外膜生态位内与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在我们未来选择血管周围时提供重要的关键 祖细胞在骨骼再生医学中的临床应用。

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.