Similar Datasets
Project description:Purpose: analyze the transcriptomic changes occurring in spleen (SP) and lymph node (LN) stromal cells in a murine model of DLBCL. Purpose: analyze the transcriptomic changes occurring in FRCs in DLBCL
2023-06-16 | GSE179193 | GEO
Project description:Tissue structure of the lymph node (LN) is supported by the network of stromal cells of mesenchymal origin, which is suggested to contribute to various immunological processes. In order to identify stromal cell–derived factors that regulate immune function, we performed gene expression profiling of stromal cells freshly isolated from collagenase digested mouse LNs, cultured stromal cell lines, and embryonic fibroblasts as a mesenchymal control.
2014-06-19 | GSE55251 | GEO
Project description:Lymph node (LN) stromal cells play a crucial role in LN development and in supporting adaptive immune responses. However, their origin, differentiation pathways, and transcriptional programs are still elusive. Here, we used lineage-tracing approaches and single-cell transcriptome analyses to determine origin, transcriptional profile, and composition of LN stromal and endothelial progenitors. Our results showed that all major stromal cell subsets and a large proportion of blood endothelial cells originate from embryonic Hoxb6+ progenitors of the lateral plate mesoderm (LPM), whereas lymphatic endothelial cells arise from Pax3+ progenitors of the paraxial mesoderm (PXM). Single-cell RNA sequencing revealed the existence of different Cd34+ and Cxcl13+ stromal cell subsets and showed that embryonic LNs contain proliferating progenitors possibly representing the amplifying populations for terminally differentiated cells. Taken together, our work identifies the earliest embryonic sources of LN stromal and endothelial cells and demonstrates that stromal diversity begins already during LN development.
2022-04-08 | GSE151623 | GEO
Project description:Tissue structure of the lymph node (LN) is supported by the network of stromal cells of mesenchymal origin, which is suggested to contribute to various immunological processes. In order to identify stromal cellM-bM-^@M-^Sderived factors that regulate immune function, we performed gene expression profiling of stromal cells freshly isolated from collagenase digested mouse LNs, cultured stromal cell lines, and embryonic fibroblasts as a mesenchymal control. Total RNAs extracted from the CD45-CD31-podoplanin+VCAM-1+ stromal cell fraction was sorted from enzymatically digested mouse LNs, cultured stromal cell lines stimulated with or without lymphotoxin (LTM-NM-2R agonistic antibody), and mouse embryonic fibroblasts (MEFs) were used for microarray analysis to assess relative gene expression.
2014-06-19 | E-GEOD-55251 | biostudies-arrayexpress
Project description:Lymph nodes (LN) are constructed of intricate networks of endothelial and mesenchymal stromal cells. These include the fibroblastic reticular cells (FRC), lymphatic endothelial cells (LEC) and blood endothelial cells (BEC). We performed a comprehensive analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly. Infection induced rapid transcriptional regulation of large numbers of both shared and unique genes in FRC, LEC and BEC to support LN remodeling and the immune response. This transcriptional program was transient, returning to homeostasis within one month of infection. Yet, expanded FRC networks persisted for greater than three months after infection. Our results reveal the complexity of LN stromal cell responses during infection and suggest that LN remodeling to acute infection supports successive immune responses.
2016-12-21 | GSE84284 | GEO
Project description:Metastatic dissemination is critically reliant on the formation of a receptive niche, a process which is thought to rely on signals derived from the primary tumor. Lymph nodes are continuously exposed to such signals through the flow of afferent lymph, allowing the potential reprograming of lymphoid tissue stroma in support of metastases or immunosuppression. We utilize single cell RNA sequencing to profile reprograming of the stromal support network within the pre-metastatic lymph node. Transcriptomic changes of the tumor-draining LN are compared against those of the contralateral non-draining LN. Additionally, we include experimental conditions for comparison in which LNs are exposed to fixed tumor cells, mimicking antigenic challenge without active tumor growth, thereby allowing us to distinguish between active tumor-elicited reprograming and general immune responses to tumor antigen.
2023-11-29 | GSE248905 | GEO
Project description:The perinatal period is a critical time-window in establishing T-cell tolerance. Regulatory T cells (Tregs) made during the first two weeks of life are key drivers of perinatal tolerance induction, but how these cells are generated and operate has not been established. To elucidate the unique environment murine perinatal Tregs encounter within the lymph nodes (LNs) as they first emerge from the thymus, and how it evolves over the succeeding days, we employed single-cell RNA sequencing to generate an atlas of the early LN niche. A highly dynamic picture emerged, the stromal-cell compartment showing the most striking changes and putative interactions with other LN cell compartments. In particular, LN stromal cells showed increasing potential for lymphocyte interactions with age. Analogous studies on mice lacking α:β T cells or enriched for autoreactive α:β T cells revealed an acute stromal-cell response to α:β T cell dysfunction, largely reflecting dysregulation of Tregs. Punctual ablation of perinatal Tregs induced stromal-cell activation that was dependent on both interferon-gamma signaling and activation of conventional CD4+ T cells. These findings elucidate some of the earliest cellular and molecular events in perinatal induction of T-cell tolerance, providing a framework for future explorations.
2023-12-27 | GSE244742 | GEO
Project description:The perinatal period is a critical time-window in establishing T-cell tolerance. Regulatory T cells (Tregs) made during the first two weeks of life are key drivers of perinatal tolerance induction, but how these cells are generated and operate has not been established. To elucidate the unique environment murine perinatal Tregs encounter within the lymph nodes (LNs) as they first emerge from the thymus, and how it evolves over the succeeding days, we employed single-cell RNA sequencing to generate an atlas of the early LN niche. A highly dynamic picture emerged, the stromal-cell compartment showing the most striking changes and putative interactions with other LN cell compartments. In particular, LN stromal cells showed increasing potential for lymphocyte interactions with age. Analogous studies on mice lacking α:β T cells or enriched for autoreactive α:β T cells revealed an acute stromal-cell response to α:β T cell dysfunction, largely reflecting dysregulation of Tregs. Punctual ablation of perinatal Tregs induced stromal-cell activation that was dependent on both interferon-gamma signaling and activation of conventional CD4+ T cells. These findings elucidate some of the earliest cellular and molecular events in perinatal induction of T-cell tolerance, providing a framework for future explorations.
2023-12-27 | GSE244741 | GEO
Project description:Gut-draining mesenteric lymph nodes (mLN) provide the framework and microenvironment to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in composition and immuno-modulatory function of SCs. Here, we dissect the tissue-specific epigenomic DNA accessibility and CpG methylation landscape of LN non-endothelial SCs and identify a microbiota-independent core epigenomic signature of LN SCs. By combined analysis of transcription factor (TF) binding sites together with the gene expression profiles of non-endothelial SCs, we delineated TFs poising skin-draining peripheral LN (pLN) SCs for pro-inflammatory responses. Furthermore, using scRNA-seq, we dissected the developmental trajectory of mLN SCs derived from postnatal to aged mice, identifying two distinct putative progenitors, namely CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid postnatal LN expansion. Finally, we identified Irf3 as a key differentiation TF inferred from the epigenomic signature of mLN SCs that is dynamically expressed along the differentiation trajectories of FRCs, and validated Irf3 as a regulator of Cxcl9+ FRC differentiation. Together, our data constitute a comprehensive transcriptional and epigenomic map of mLN development and dissect location-specific, microbiota-independent properties of mLN non-endothelial SCs. As such, our findings represent a valuable resource to identify core transcriptional regulators that impinge on the developing mLN early in life, thereby shaping long-lasting intestinal adaptive immune responses.
2022-10-07 | GSE171897 | GEO
Project description:Gut-draining mesenteric lymph nodes (mLNs) provide the framework to shape intestinal adaptive immune responses. We previously delineated transcriptional signatures in LN stromal cells (SC), pointing to tissue-specific variability in SC composition and immunomodulatory function. Here, using scRNA-seq we dissected the developmental trajectory of SCs within mLNs derived from postnatal to aged mice, and identified two putative progenitors, namely CD34+ SC and fibroblastic reticular stromal cell (FRC) progenitors, which both feed the rapid LN expansion postnatally. We further unraveled the tissue-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs, and identified a microbiota-independent core epigenomic signature, showcasing differences between SCs from mLN and skin-draining peripheral LN. Irf3 was inferred from the epigenomic landscape of SCs, being dynamically expressed along the differentiation trajectories of FRCs. Lentiviral overexpression of Irf3 in a mesenchymal stem cell line established a Cxcl9+ FRC molecular phenotype. The relevance of Irf3 for SC biology was further underscored by the diminished proportion of Ccl19+ and Cxcl9+ FRCs in LNs from Irf3-/- mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.
2022-10-07 | GSE171905 | GEO