Context-Dependent Development of Lymphoid Stroma from Adult CD34+ Adventitial Progenitors

Abstract

Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3(-)PDPN(+)PDGFRβ(+)/α(+)CD34(+) stromal adventitial cells in both lymph nodes (LNs) and thymus that is located within the vascular niche surrounding PDPN(-)PDGFRβ(+)/α(-)Esam-1(+)ITGA7(+) pericytes. CD34(+) adventitial cells developed in late embryonic thymus and in postnatal LNs and in the thymus originated, along with pericytes, from a common anlage-seeding progenitor population. Using lymphoid organ re-aggregate grafts, we demonstrate that adult CD34(+) adventitial cells are capable of differentiating into multiple lymphoid stroma-like subsets including pericyte-, FRC-, MRC-, and FDC-like cells, the development of which was lymphoid environment-dependent. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34(+) adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues.

Perivascular Fibroblasts of the Developing Spleen Act as LTα1β2-Dependent Precursors of Both T and B Zone Organizer Cells

“…Of note, in the few LNs developing in Cxcl13 À/À mice, the early T-B accumulation and segregation occur normally, including LTa1b2 expression on Cxcr5 À/À ILC3, with only the later development of FDCs and polarized follicles being defective (Cupedo et al, 2004;Luther et al, 2003). We propose that CCR7 on B cells may compensate for CXCR5 deficiency by positioning them next to the central arteriole, where we observed CCL21 expression and perivascular mesenchymal cells that may act as LTa1b2-dependent precursor cells (Sitnik et al, 2016).…”

Global transcriptomic profiling of the bone marrow stromal microenvironment during postnatal development, aging and inflammation

“…In periarterial bundles, PαSc lie adjacent to, but are distinct from smooth muscle actin cells and Nestin-GFP cells (not shown) and can be distinguished by expression of CD34. Altogether these findings lead us to speculate that PαSc potentially represent a distinct lineage of mesenchymal stromal precursors equivalent to those recently found in the adventitial cuffs of multiple organs (Sitnik et al, 2016). Of interest, recent work suggests a central role of these CD140b + Sca-1 + Pdpn + in the maintenance of type 2 innate lymphoid cell (ILC-2) within defined periarterial niches of lung and adipose tissues via expression of IL-33 (Dahlgren et al, 2019;Mahlakõiv et al, 2019;Spallanzani et al, 2019).…”

Phenotypically heterogeneous podoplanin-expressing cell populations are associated with the lymphatic vessel growth and fibrogenic responses in the acutely and chronically infarcted myocardium

“…We found by flow-cytometry analysis of cardiac cells from acutely infarcted hearts (S4 Fig), and immunohistochemistry assessment of myocardium at the different times after MI (Fig 6A–6C, white arrowheads, and Fig 6C graph), that the podoplanin-presenting cells in the infarcted heart were distinctly PDGFRα-positive. Since PDGFRα expression is associated with the properties of immature mesenchymal cells [35–39], the concordance of PDGFRα and podoplanin staining suggests that cardiac podoplanin-positive cells contain a population with progenitor cell capabilities.…”