Over expression of MHC Class l protein in skeletal muscle causes myositis. Phenotype after expression in young mice is more severe.
Overexpression of MHC class I heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis.
Sex, Specimen part, Treatment
View SamplesPosterior embryonic axis develops from neuromesodermal progenitors which differentiate into neural tube and paraxial mesoderm
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Treatment
View SamplesCD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150).
Specimen part
View SamplesThe satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We have carried out transcriptome analyses by comparing satellite cells from adult skeletal muscles, where they are mainly quiescent, with cells from growing muscles, regenerating (mdx) muscles, or with cells in culture, where they are activated. Our study gives new insights into the satellite cell biology during activation and in respect with its niche.
An adult tissue-specific stem cell in its niche: a gene profiling analysis of in vivo quiescent and activated muscle satellite cells.
Specimen part
View SamplesCD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation.
Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150).
Specimen part
View SamplesCell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage.
Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
Specimen part, Cell line
View SamplesHepatoblastoma (HB) is the most common pediatric liver tumor, and there are no targeted therapies available for children with HB. We have previously developed a murine model of HB which is driven by coactivation of the oncogenes YAP1 and -catenin (CTNNB1) [Tao J, Calvisi D, Ranganathan S, et al. Gastroenterology, 2014 Sep; 147(3): 690701]. We used the Sleeping Beauty transposase system combined with hydrodynamic tail vein injection to deliver plasmids containing mutant activated forms of YAP1 (YAP S127A) and -catenin (N90 -catenin) to a small number of pericentral hepatocytes. We have shown that these few transformed hepatocytes proliferate and dedifferentiate, eventually forming histologically heterogeneous tumors that resemble various subtypes of human HB (which is also highly heterogeneous), including areas of well-differentiated fetal, crowded fetal, embryonal, and blastemal HB. Our goal was to investigate how coactivation of YAP1 and -catenin drive the dedifferentiation of hepatocytes into hepatoblast-like tumor cells over time, leading to HB tumors. In order to measure changes in gene expression during tumorigenesis in our model, we used an Affymetrix microarray to analyze isolated RNA from wild type FVB mouse livers, mouse HB tumor tissue, and non-tumor liver tissue adjacent to HB tumors.
Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma.
Age, Specimen part
View SamplesThe Rift Valley Fever (RVF) is an arthropod-borne disease present in several countries of Africa and Middle East. It is caused by RVF virus which can infect both humans and animals. In humans, it leads to various manifestations including hepatitis, encephalitis and death, while in domestic animals it usually causes miscarriage in pregnant females and it is often fatal for the newborn. Not all people or animal infected by the virus present the same disease. Some patients exhibit unapparent or moderate febrile reactions, while others develop severe symptoms. This observation suggests that host genetic factors play a role in controlling the outcome of infection. In this work, we compare the response of two different inbred strains of mice, MBT/Pas and BALB/cByJ, to infection with RVF virus. These strains exhibit different profiles of susceptibility to RVF virus infection. Indeed, MBT/Pas mice rapidly develop high viraemia and die soon after infection, while BALB/cByJ mice have a lower viraemia and die later. Interestingly, mouse embryonic fibroblasts (MEFs) obtained from MBT/Pas foetuses allows higher viral production than BALB/cByJ MEFs.
A new mouse model reveals a critical role for host innate immunity in resistance to Rift Valley fever.
Specimen part
View SamplesThe generation of specific types of neurons from stem cells offers important opportunities in regenerative medicine. However, future applications and proper verification of cell identities will require stringent ways to generate homogenous neuronal cultures. Here we show that under permissive culturing conditions individual transcription factors can induce a desired neuronal lineage from virtually all expressing cells by a mechanism resembling developmental binary cell fate switching. Such efficient selection of cell fate resulted in remarkable cellular enrichment that enabled global gene expression validation of generated neurons and identification of novel features in the studied cell lineages. Several sources of stem cells have a limited competence to differentiate into e.g. dopamine neurons. However, we show that the combination of factors that normally promote either regional or dedicated neuronal specification can overcome limitations in cellular competence and promote efficient reprogramming also in more remote neural contexts, including human neural progenitor cells.
Transcription factor-induced lineage selection of stem-cell-derived neural progenitor cells.
Specimen part, Cell line
View SamplesA genetic association between the ANP32A gene and osteoarthritis has been suggested. We compared transcriptome profiles of the articular cartilage and subchondral bone from mice deficient in ANP32A with wild-type mice to get insights into the role of ANP32A in the pathogenesis of ostearthritis.
ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone.
Age, Specimen part
View Samples