Th1 cells are critical tissue organizers of myeloid-rich perivascular activation niches
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PROVIDER: PRJNA1235719 | ENA |
REPOSITORIES: ENA
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Project description:Aggregating immune cells within perivascular niches (PVN) can regulate tissue immunity in infection, autoimmunity and cancer. How cells are assembled at PVNs and the activation signals imparted within remain unclear. Here, we integrate dynamic time-resolved in vivo imaging with a novel spatially-resolved platform for microanatomical interrogation of transcriptome, immune phenotype and inflammatory mediators in skin PVNs. We uncover a complex positive-feedback loop within CXCL10+PVNs that regulates myeloid and Th1 cell positioning for exchange of critical signals for Th1 activation. Th1 cells spend ∼24h in the PVN, receiving initial peripheral activation signals, before redeploying to the inflamed dermal parenchyma. Niche-enriched, CCR2-dependent myeloid cells were critical for Th1 IFNγ-production. In turn, PVN instructional signals enabled Th1s to orchestrate PVN assembly by CXCR2-dependent intra-tissue myeloid cell aggregation. The results reveal a critical tissue organizing role for Th1s, gained rapidly on tissue entry, that could be exploited to boost regional immunity.
2025-04-07 | GSE291886 | GEO
Project description:Effect of bioengineered niches on perivascular stem cell phenotype.
| PRJNA1104214 | ENA
Project description:Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via allogeneic stem cell transplantation (alloSCT), to engraft and repopulate the blood system. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs (ST-HSC) and progenitor populations at the expense of naïve LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs or pericytes). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1 expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1 expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.
2024-04-25 | GSE265789 | GEO
Project description:The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5+) and non-perivascular (W5C5-) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5+ to W5C5- cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5+ progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5+-derived cells produced lower levels of various chemokines and inflammatory modulators when compared to their W5C5- counterparts. This divergence in secretomes became more pronounced upon decidualization, which transformed perivascular W5C5+ cells into the dominant source of a range of trophic and immunomodulatory cytokines, including leukemia inhibitory factor (LIF). Our findings indicate that the decidual response is spatially organized with differentiating perivascular cells establishing distinct cytokine and chemokine gradients that could direct trophoblast towards maternal vessels and govern local immune responses in pregnancy. Analysis of paired human endometrial stromal cultures, originating from either W5C5+ or W5C5- cells, from four biological replicates - a total of 8 samples - by Illumina RNAseq.
2014-10-29 | E-GEOD-57182 | biostudies-arrayexpress
Project description:Aim of this experiment was to characterize whether SPP1 released from the hippocampal perivascular space could imprint microglia transcriptional states. We performed scRNA-seq analysis on sorted CD140a+ perivascular fibroblast (PVF), CD45highCD11intCD206+ perivascular macrophage (PVM) and CD45intCD11intCX3CR1high microglial cell from dissected hippocampi of 6-month old wild type vs SPP1KO/KO vs AppNL-F mice vs AppNL-FxSpp1KO/KO mice. Cells were isolated from dissected hippocampi as previously described (Sala Frigerio et al.,2019).
2024-02-09 | E-MTAB-11918 | biostudies-arrayexpress
Project description:The bone tissue undergoes constant turnover, which relies on skeletal stem cells (SSCs) and/or mesenchymal stem cells (MSCs) and their niches. SSCs/MSCs and their perivascular niche within the bone marrow are well characterized in long bones. As for cranial bones, besides bone marrow, the suture mesenchyme has been identified as a unique niche for SSCs/MSCs of craniofacial bones. However, a comprehensive study of the two different cranial stem cell niches at single-cell resolution is still lacking. In addition, during the progression of aging, age-associated changes in cranial stem cell niches and resident cells remain uncovered. In this study, we investigated age-related changes in cranial stem cell niches via single-cell RNA sequencing (scRNA-seq).
2023-09-11 | GSE235176 | GEO
Project description:Glioblastoma stem cells (GSCs) have been reported to be found near the blood vessels. We wanted to identify the perivascular GSCs by combining the label retention approach with vascular perfusion. GSCs, like most of the stem cells, are in a quiescent state. Label retention approach involves staining the cells with a uniform membrane labeling dye (PKH26) and allowing them to grow in vivo in NOD SCID mice. Slow-dividing stem cells will retain the dye to a greater extent and perivascular cells are identified by injecting the mice with vascular perfusion dye (Hoechst 33342) 5 min prior to sacrifice. Perivascular GSCs (positive for Hoechst 33342 and pKH26 dye - dubbed as H+P+) were compared with the rest of the perivascular glioma cells (H+P-).
2022-01-01 | E-MTAB-9607 | biostudies-arrayexpress
Project description:The role of perivascular cell heterogeneity in tumor metastasis remains unknown. Here, we dissected the heterogeneity of perivascular cells by single-cell RNA sequencing and defined 13 subpopulations of pericytes within human colorectal cancers (CRC). Among them, an extracellular matrix (ECM)-rich subpopulation of TCF21high tumor pericytes (TPCs) was identified, which highly correlated with metastatic potentials in human CRC patients. Pericyte-specific conditional deletion of Tcf21 in mice mitigated CRC metastasis by decreasing perivascular ECM resmodeling, maintaining the integrity of the basement membrane, and reducing circulating cancer cells. Conversely, co-injection of CRC cells with TCF21high TPCs markedly promoted metastasis. Mechanistically, high expression of TCF21 in TPCs altered ECM stiffness, collagen deposition/rearrangement, and basement membrane degradation, which collectively instigated tumor cell intravasation and metastasis. Compelling experimental evidence showed that the loss of integrin α5 activated the FAK/PI3K/AKT axis, impaired DNA hypermethylation of TCF21, leading to high expression of TCF21 in TPCs. Our data provide new mechanistic insights into functions of a specific subpopulation of perivascular cells in promoting cancer metastasis and therapeutic targeting of metastasis-promoting TPCs may provide a new paradigm for cancer therapy.
2023-03-01 | GSE199726 | GEO
Project description:The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5+) and non-perivascular (W5C5-) fibroblasts from mid-luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5+ to W5C5- cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5+ progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5+-derived cells produced lower levels of various chemokines and inflammatory modulators when compared to their W5C5- counterparts. This divergence in secretomes became more pronounced upon decidualization, which transformed perivascular W5C5+ cells into the dominant source of a range of trophic and immunomodulatory cytokines, including leukemia inhibitory factor (LIF). Our findings indicate that the decidual response is spatially organized with differentiating perivascular cells establishing distinct cytokine and chemokine gradients that could direct trophoblast towards maternal vessels and govern local immune responses in pregnancy.
2014-10-29 | GSE57182 | GEO
Project description:Inflammatory crosstalk between perivascular adipose tissue and and blood vessel wall may contribute to atherosclerosis pathogenesis, and exhibits more pro-inflammatory than adipogenic phenotype than subcutaneous adipocytes. To identify a genomic basis for biologic differences, we performed genome-wide expression to identiy expression genes differentially regulated between perivascular and subcutaneous adipocytes.for biologic differences. We performed global gene expression analyses on in vitro differentiated adipocytes from human left coronary artery perivascular adipose tissue and subcutaneous adipose tissues derived from unrelated donors who were non-obese and did not have any known metabolic or atherosclerotic disease.
2013-03-15 | E-GEOD-45169 | biostudies-arrayexpress