Project description:Investigate detailed cellular composition of the LAM lung compared to the age and sex matched healthy control, in order to isolate LAM-lung-specific cellular states or subtypes.
Project description:Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by smooth, muscle-like LAM cells which have mutations in the tumor suppressor genes Tuberous Sclerosis Complex (TSC) 1 or 2, and the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of MCP-1/CCL2, GROa/CXCL1 and ENA-78/CXCL5 were significantly higher in samples from LAM patients than healthy volunteers. In this transcript analysis, expression of chemokine and chemokine receptor mRNA in LAM cells differed from those in melanoma and smooth muscle cells. Subsequent immunohistochemistry of lung sections from 30 LAM patients confirmed protein expression of chemokines and these receptors varied among LAM patient and differed from that seen in breast cancer and melanoma cells. . In vitro, MCP-1/CCL2 induced selective migration of cells showing loss of heterozygosity of TSC2 from a heterogeneous populations of cells grown from explanted LAM lungs. In addition, the frequencies of single-nucleotide polymorphisms in the MCP-1 gene promoter region differed significantly in LAM patients and healthy volunteers (p=0.018), and one polymorphism was associated significantly more frequently with the decline of lung function. These observations are consistent with the notion that chemokines such as MCP-1 may serve to specify site of LAM cell metastasis. Keywords: Human patient sample comparison with cell lines The study is of case/control design with biological replication. Biopsies of nodules from 14 LAM patients (cases) are compared with cultured cell lines (controls) with similar properties.
Project description:Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by smooth, muscle-like LAM cells which have mutations in the tumor suppressor genes Tuberous Sclerosis Complex (TSC) 1 or 2, and the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of MCP-1/CCL2, GROa/CXCL1 and ENA-78/CXCL5 were significantly higher in samples from LAM patients than healthy volunteers. In this transcript analysis, expression of chemokine and chemokine receptor mRNA in LAM cells differed from those in melanoma and smooth muscle cells. Subsequent immunohistochemistry of lung sections from 30 LAM patients confirmed protein expression of chemokines and these receptors varied among LAM patient and differed from that seen in breast cancer and melanoma cells. . In vitro, MCP-1/CCL2 induced selective migration of cells showing loss of heterozygosity of TSC2 from a heterogeneous populations of cells grown from explanted LAM lungs. In addition, the frequencies of single-nucleotide polymorphisms in the MCP-1 gene promoter region differed significantly in LAM patients and healthy volunteers (p=0.018), and one polymorphism was associated significantly more frequently with the decline of lung function. These observations are consistent with the notion that chemokines such as MCP-1 may serve to specify site of LAM cell metastasis. Keywords: Human patient sample comparison with cell lines
Project description:Nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in the NP tissue during IVDD progression. Here, we used single cell RNA sequencing (scRNA-seq) to analyze the cellular and molecular alterations of diverse cell clusters during IVDD.
Project description:Obstructive Sleep Apnea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioral, metabolic, and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined. scRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs.