Similar Datasets
Project description:Disseminated cancer cells reside in the lung alveolar niche where they are exposed to interactions with alveolar macrophages. Here we report bulk RNA-sequencing data from co-cultured MMTV-HER2 mammary early lesion cells or mammary primary tumor cells cultured with lung alveolar macrophages. We discovered reciprocal regulation between mammary cells and alveolar macrophages, where early lesion cells instruct alveolar macrophages to maintain an anti-tumor phenotype and alveolar macrophages activate an epithelial to mesenchymal program in early lesion cells. Coveresely, primary tumor cells activate inflammatory prorgams in alveolar macrophages, while alveolar macrophages are not able to activate growth restriction programs in primary tumor cells. Receptor-ligand analysis highlighted two known pathways invovled in quiencesce, namely the TGF-beta pathway and the OSM pathway.
2024-09-30 | GSE278443 | GEO
Project description:The effect of co-culture on MMTV-HER2 early lesion or primary tumor cell and alveolar macrophages
| PRJNA1167295 | ENA
Project description:The effect of co-culture on MMTV-HER2 early lesion or primary tumor cell and alveolar macrophages [bulk RNA-seq]
| PRJNA1167276 | ENA
Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation.
2021-01-26 | GSE165431 | GEO
Project description:Cancer cells can disseminate from early-evolved primary lesions. It is thought that a state of early disseminated cancer cell (early DCC) dormancy would precede genetic maturation of DCCs and metastasis initiation. Here we reveal at single cell resolution a previously unrecognized role of mesenchymal- and pluripotency-like programs in coordinating early cancer cell spread and a long-lived dormancy program in early DCCs. We identify in early lesions and early DCCs, the transcription factor ZFP281 as an inducer of mesenchymal- and primed pluripotency-like programs, which is absent in advanced primary tumors and overt metastasis. ZFP281 not only controls the early spread of cancer cells but also locks early DCCs in a prolonged dormancy state by preventing the acquisition of an epithelial-like proliferative program. Thus, ZFP281-driven dormancy of early DCCs may be a rate-limiting step in metastatic progression functioning as a first barrier that DCCs must overcome to then undergo genetic maturation. This data set aims identify ZFP281 targets in MMTV-Neu early lesion (EL) and primary tumor (PT) cells
2021-01-26 | GSE165444 | GEO
Project description:Type I alveolar epithelial cells (ATIs) are very large, thin cells, which extend across several air sacs and cover more than 95% of the alveolar surface area. ATIs are the target of many insults, including ventilator-induced lung injury, and are generally considered terminally differentiated cells arising from type II cell (ATII) lineage. ATIs have proven difficult to harvest and maintain in primary culture, which is why much of ATI biology has been inferred from studies on ex vivo, ATII-derived, so-called ATI-like cells. We report on a modified approach to rat ATI harvest and primary culture, which yielded the following observations: (1) rat ATI can be harvested and maintained with a high degree of purity in primary culture; (2) in vitro growth characteristics of primary ATIs differ from those of ATII-derived ATI-like cells; ATIs, but not ex vivo, ATII-derived ATI-like cells, are capable of cell division; (3) ATIs readily repair plasma membrane wounds without the subsequent loss of their ability to divide; (4) ATI monolayers heal scratch wounds primarily by cell spreading and migration. Although the ability of ATIs to divide may be limited to the in vitro environment, we do believe that their role in alveolar wound repair deserves to be revisited, and the molecular control of ATI-ATII plasticity further explored.
| S-EPMC3095986 | biostudies-literature
Project description:Senescent cells play relevant but context-dependent roles during tumorigenesis. Here, in an oncogenic Kras-driven lung cancer mouse model, we found that senescent cells, specifically alveolar macrophages, accumulate early in neoplasia. These macrophages have upregulated expression of p16INK4a and Cxcr1, are distinct from previously defined subsets and are sensitive to senolytic interventions, and suppress cytotoxic T cell responses. Their removal attenuates adenoma development and progression in mice, indicating their tumorigenesis-promoting role. Importantly, we found that alveolar macrophages with these properties increase with normal aging in mouse lung and in human lung adenocarcinoma in situ. Collectively, our study indicates that a subset of tissue-resident macrophages can support neoplastic transformation through altering their local microenvironment, suggesting that therapeutic interventions targeting senescent macrophages may attenuate lung cancer progression during early stages of disease.
| S-EPMC10524974 | biostudies-literature
Project description:Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells.
| S-EPMC4393197 | biostudies-other
Project description:In vitro co-cultures of different primary human cell types are pivotal for the testing and evaluation of biomaterials under conditions that are closer to the human in vivo situation. Especially co-cultures of macrophages and mesenchymal stem cells (MSCs) are of interest, as they are both present and involved in tissue regeneration and inflammatory reactions and play crucial roles in the immediate inflammatory reactions and the onset of regenerative processes, thus reflecting the decisive early phase of biomaterial contact with the host. A co-culture system of these cell types might thus allow for the assessment of the biocompatibility of biomaterials. The establishment of such a co-culture is challenging due to the different in vitro cell culture conditions. For human macrophages, medium is usually supplemented with human serum (hS), whereas hMSC culture is mostly performed using fetal calf serum (FCS), and these conditions are disadvantageous for the respective other cell type. We demonstrate that human platelet lysate (hPL) can replace hS in macrophage cultivation and appears to be the best option for co-cultivation of human macrophages with hMSCs. In contrast to FCS and hS, hPL maintained the phenotype of both cell types, comparable to that of their respective standard culture serum, as well as the percentage of each cell population. Moreover, the expression profile and phagocytosis activity of macrophages was similar to hS.
| S-EPMC6401182 | biostudies-other
Project description:The intracellular bacterial pathogen Coxiella burnetii is a category B select agent that causes human Q fever. In vivo, C.?burnetii targets alveolar macrophages wherein the pathogen replicates in a lysosome-like parasitophorous vacuole (PV). In vitro, C.?burnetii infects a variety of cultured cell lines that have collectively been used to model the pathogen's infectious cycle. However, differences in the cellular response to infection have been observed, and virulent C.?burnetii isolate infection of host cells has not been well defined. Because alveolar macrophages are routinely implicated in disease, we established primary human alveolar macrophages (hAMs) as an in vitro model of C.?burnetii-host cell interactions. C.?burnetii pathotypes, including acute disease and endocarditis isolates, replicated in hAMs, albeit with unique PV properties. Each isolate replicated in large, typical PV and small, non-fused vacuoles, and lipid droplets were present in avirulent C.?burnetii?PV. Interestingly, a subset of small vacuoles harboured single organisms undergoing degradation. Prototypical PV formation and bacterial growth in hAMs required a functional type IV secretion system, indicating C.?burnetii secretes effector proteins that control macrophage functions. Avirulent C.?burnetii promoted sustained activation of Akt and Erk1/2 pro-survival kinases and short-termphosphorylation of stress-related p38. Avirulent organisms also triggered a robust, early pro-inflammatory response characterized by increased secretion of TNF-? and IL-6, while virulent isolates elicited substantially reduced secretion of these cytokines. A corresponding increase in pro- and mature IL-1? occurred in hAMs infected with avirulent C.?burnetii, while little accumulation was observed following infection with virulent isolates. Finally, treatment of hAMs with IFN-? controlled intracellular replication, supporting a role for this antibacterial insult in the host response to C.?burnetii. Collectively, the current results demonstrate the hAM model is a human disease-relevant platform for defining novel innate immune responses to C.?burnetii.
| S-EPMC3655087 | biostudies-literature