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Integrated transcriptomics of human blood vessels defines the spatially regulated niche for early mesenchymal progenitors

ABSTRACT: Blood vessel walls are organized into concentric cellular layers, in which the outer layer, or tunica adventitia, represents the major niche for mesenchymal progenitor cells. By profiling large vessels (arteries and veins) using spatial transcriptomics, we found a hierarchy of stem cells based on spatial organization. In addition, we performed scRNaseq on CD34+ adventitial cells and integrated to out spatial transcriptomics where we identified the novel stem cell marker CD201 in the outer layer. This segregation was regulated by the WNT and TGFβ signaling pathways, which was confirmed by total RNAseq of CD201Low/High subsets of adventitial cells. To investigate the transcriptomic differences between the novel subset of of adventitial cells (CD34+,CD31-,CD45-) based on CD201 expression, FACTS isolated adventitial cells with low /high CD201 expression were sequenced.

ORGANISM(S): Homo sapiens

PROVIDER: GSE217216 | GEO | 2024/05/29

REPOSITORIES: GEO

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Project description:Despite their key role in immunity our understanding of primary and secondary lymphoid stromal cell heterogeneity and ontogeny remains limited. Here, using genome-wide expression profiling and phenotypic and localization studies, we identify a functionally distinct subset of BP3-PDPN+PDGFRÎ²+/Î±+CD34+ stromal adventitial cells in both lymph nodes and thymus that is located within the perivascular niche surrounding PDPN-PDGFRÎ²+/Î±-Esam-1+ITGA7+ pericytes. In re-aggregate organ grafts adult CD34+ adventitial cells gave rise to multiple thymic and lymph node mesenchymal subsets including pericytes, FRC-, MRC- and FDC-like cells, the development of which was lymphoid environment dependent. During thymic ontogeny pericytes developed from a transient population of BP3-PDPN+PDGFRÎ²+/Î±+CD34-/lo anlage-seeding progenitors that subsequently up-regulated CD34 and we provide evidence suggesting that similar embryonic progenitors give rise to lymph node mesenchymal subsets. These findings extend the current understanding of lymphoid mesenchymal cell heterogeneity and highlight a role of the CD34+ vascular adventitia as a potential ubiquitous source of lymphoid stromal precursors in postnatal tissues. To comprehensively study the differences and similarities between mesenchymal stromal subsets in the thymus and lymph nodes, global gene expression analysis was performed on sorted PDPN-, BP-3-PDPN+ and BP-3+PDPN+ PDGFRb+ lymph node mesenchymal cells (LNMC) as well as PDPN- and BP-3-PDPN+ PDGFRb+ thymic mesenchymal cells (TMC) from 2 w old mice by microarray. Total RNA was prepared from TMC and LNMC (pooled inguinal, brachial and axillary LN) subsets sorted from 3 (TMC) and 10-11 (LNMC) 2 weeks old mice per experiment. Isolated RNA from 3 individual experiments was amplified and prepared for hybridization to the Affymetrix Mouse Gene 1.1 ST Array at a genomics core facility: Center of Excellence for Fluorescent Bioanalytics (KFB, University of Regensburg, Germany)

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Integrated transcriptomics of human blood vessels defines the spatially regulated niche for early mesenchymal progenitors

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