Defining the human adventitial stem cell niche

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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.