Defining the human adventitial stem cell niche

项目摘要 维管树精细地组织成同心的层，最外层称为图尼卡 外膜脂肪组织内的多能祖细胞的大部分位于外膜内，而细胞外膜内的多能祖细胞的大部分位于外膜内。 这个干细胞生态位的多样性现在才被发现。我们的实验室已经证明了一种有前途的 FACS纯化的人外膜细胞（外膜细胞）诱导和参与骨再生的作用 (Wang例如，NPJ Regen Med 2018）。尽管外膜位置保守，但当血管周围细胞 用组学方法研究，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，以进一步确定CD34+的干细胞层次 外膜细胞（Xu等人，Elife 2020）。我们最近的研究结果表明，一个连续的细胞类型存在于这个 显微解剖干细胞龛，新的细胞表面标志物突出了组织学上的不同， 功能相关的外膜亚群（Ding等人，干细胞2020）。 目前的探索性建议利用了这一系列的意见，首次寻求审查 人类脂肪组织外膜小生境内功能相关的细胞多样性。我们希望 这里概述的概念验证研究将为我们未来选择血管周围治疗提供重要的关键 用于骨骼再生医学的临床应用的祖细胞。

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.