Global gene experssion study of the HAEC transcriptional response to artificial chlyomicron remnant-like particles (A-CRLPs) prepared with triglycerides extracted from four natural dietary oils: fish, DHASCO, corn and palm oils.  We hypothesised that A-CRLPs could differentially regulate HAEC gene expression according to thier triglyceride content.  These data provide an important starting point for investigations into the effects of A-CRLPs on endothelial cells, particulary genes involved in redox balance and inflammatory processes.

Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway.

Effects of model chylomicron remants on gene expresssion in human aortic endothelial cells (HAEC)

We conducted a genetic analysis of the developing temporo-mandibular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw.  First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared to other synovial joints including the shoulder joint and the hip joint. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the Hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth plate-like cellular organization and no disk is formed. In addition, we utilized a conditional strategy to remove activity of the Hh co-receptor encoded by Smo from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle.  Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation and disk-condyle separation, and provide a molecular framework for future studies of the TMJ.

Temporomandibular joint formation requires two distinct hedgehog-dependent steps.

RNA expression data of embryonic E16.5 mouse temporomandibular joint (TMJ)

Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. We used gene expression profiling to establish a molecular definition of hepatitis B virus (HBV)-associated ALF. Two patients who underwent liver transplantation for HBV-associated ALF were studied. Gene expression profiling was performed on 8 liver specimens obtained from the two patients with ALF (4 samples per liver) and individual liver specimens from 8 liver donors and normal livers from 11 patients who underwent resection for angioma. Statistical analyses were used to identify the signature genes of HBV-associated ALF. Multivariate permutation analysis identified 1,368 transcripts that were differentially expressed in ALF; 709 were up-regulated and 659 down-regulated. The most represented up-regulated transcripts were those involved in the immune response, whereas the most abundant down-regulated transcripts were those involved in metabolism and hepatic synthesis. ALF was characterized by overriding B-cell signature comprising genes related to mature B cells and plasma cells with abundant polyclonal expression of immunoglobulin genes.  By contrast, there was a limited T-cell signature and up-regulation of several inhibitors of T-cell activation. Immunohistochemical analysis confirmed the prominent B-cell signature showing diffuse liver infiltration by plasma blasts and plasma cells with strong cytoplasmic staining for IgM and IgG, associated with a significant deposition of complement factors. Using phage display technology, we demonstrated that the molecular target of the massive intrahepatic antibody response is the hepatitis B core antigen (HBcAg). These data suggest that the humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF.

B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure.

B-Cell Gene Signature with Massive Intrahepatic Production of Antibodies to Hepatitis B Core Antigen in HBV-Associated Acute Liver Failure

We aimed to determine the characteristic of 3 different ILC subsets (ILC1, 2 and 3) isolated from human blood. Overall design: mRNA profile of ILC1, ILC2 and ILC3

Gene expression signatures of circulating human type 1, 2, and 3 innate lymphoid cells.

Gene expression signatures of innate lymphoid cells from human blood

To investigate the role of viral and host factors in acute liver failure, we analyzed serum and multiple liver specimens obtained at the time of liver transplantation from four well-characterized patients. We carried out an integrated clinicopathological analysis, gene and microRNA expression profiling, next-generation sequencing, antibody-displaying phage libraries, and in vitro functional analysis of HBV variants.

Role of humoral immunity against hepatitis B virus core antigen in the pathogenesis of acute liver failure.

Role of Humoral Immunity against Hepatitis B Virus Core Antigen in the Pathogenesis of Acute Liver Failure

NMuMG is an epithelial cell line that can be induced into EMT by TGF- treatment or MET by TGF- withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype.

Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin β4.

Gene expression in epithelial, EMT (epithelial-mesenchymal transition) and MET (mesenchymal-epithelial transition) cells

Purpose: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets.  Methods: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 158 TN tumors (54 AA) from The Cancer Genome Atlas (TCGA). Meta-analyses were performed to obtain summary estimates by combining TCGA and Detroit AA cohort results.  Results: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR)=1.56, 95% confidence interval (CI) 1.31-1.86, nominal p=5.1x10-7, FDR p=0.014], SPIC [HR=1.47, 95%CI 1.26-1.73, nominal p=1.8x10-6, FDR p=0.022], and MIR4311 [HR=1.57, 95% CI 1.31-1.92, nominal p=2.5x10-5, FDR p=0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. Meta-analysis with TCGA data showed that CLCA2 and SPIC were associated with overall survival for TNBC among AA women.  Conclusions: We identified three potential prognostic markers for TNBC in AA women, for which SPIC may be an AA-specific prognostic marker.

CLCA2 expression is associated with survival among African American women with triple negative breast cancer.

Whole genome expression profiling of triple negative breast tumors in 226 African American women

We compared the transcriptome at gene expression level in hypoxic and normoxic conditions.

Continuous hypoxic culturing of human embryonic stem cells enhances SSEA-3 and MYC levels.

Comparison of hypoxia (4 % O2) cultured human embryonic stem cells (hESCs) to normoxia (21 % O2) cultured

CD138+ B220- plasma cells were sorted from bone marrow and B220+ CD23+ mature follicular B cells were sorted from the spleens.  Plasma cells were sorted from C57BL/6 mice 7 days after boosting with antigen, with mice first primed with an i.p. injection of KLH/IFA followed by boost at day 21 with KLH/PBS i.p. Mature B cells were sorted from antigen-nave C57BL/6 mice.

Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells.

Expression data from murine bone marrow-resident plasma cells and spleen mature follicular B cells

Mice have been treated with NOX-A12. Whole BM cells have been harvested, RNA isolated,  and gene expression profiling was performed on cDNA using Mouse Genome 430 2.0 array. Untreated mice have been used as control.