Project description:The combined activation of KrasG12D and loss of Cdkn2a leads to aggressive angiosarcomas in aP2-Cre mice. Whereas, the conditional deletion of Tsc1 leads to vascular tumor formation that mimic human kaposiform hemangioendotheliomas. We used Affymetrix microarrays to compare angiosarcoma tumors with the combined activation of KrasG12D and loss of Cdkn2a and the conditional deletion of Tsc1
Project description:Lung cancers exhibit pronounced functional heterogeneity, confounding precision medicine. We studied how the cell-of-origin contributes to phenotypic heterogeneity following conditional expression of KrasG12D and loss of Lkb1 (Kras;Lkb1). Using progenitor cell type-restricted adenoviral-Cre to target cells expressing Surfactant Protein C (SPC) or club cell antigen 10 (CC10), we show that Ad5-CC10-Cre infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. We further demonstrate that CC10+ cells are the predominant progenitors of adenosquamous carcinoma (ASC) tumors, and give rise to a wider spectrum of histotypes that includes mucinous and acinar adenocarcinomas. Transcriptome analysis shows ASC histotype-specific upregulation of proinflammatory and immunomodulatory genes. This is accompanied with an ASC-specific immunosuppressive environment, consisting of downregulated MHC genes, recruitment of CD11b+ Gr-1+ tumor-associated neutrophils (TANs) and decreased T-cell numbers. We conclude that progenitor cell-specific etiology influences the Kras;Lkb1-driven tumor histopathology spectrum and histotype-specific immune microenvironment.
Project description:Sporozoite-specific genes were induced in parasites that express AP2-O whose AP2 domain was swapped with that of AP2-Sp. DNA construct encoding AP2 domain of AP2-Sp was introduced into P. bergei schizonts. It was integrated into the locus of the endogenious AP2-O gene, resulting in swap of the AP2-domain (AP2-O::Sp parasites). Gene expression was analyzed in ookinetes cultured for 20h.
Project description:Adipose tissue is an active producer of lactate. In obesity, the increased size of adipocytes is accompanied by an increase in lactate production in adipose tissue, caused by hypoxia in obese adipocytes. How lactate affects metabolism in adipocyte and insulin sensitivity remains unclear. Here we develop a mouse model of MCT1,coding by Slc16a1, specific deletion in adipose tissues, using the AP2 promoter to drive Cre expression. This MCT1 AKO mice develop more severe insulin resistance in obesity with 16 weeks high fat diet treatment, while few changes happen to lipid metabolism in adipose tissues. We used RNA-seq to analyze the gene expression patterns of eWAT of obese MCT1 AKO mice compared to WT, and found significant changes in innate immune signaling and adipocyte apoptosis that reflect systemic inflammation and insulin resistance.
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
Project description:Dicer1 loss in the aP2-lineage leads to the development of aggressive and highly penetrant angiosarcomas independent of other oncogenes or tumor suppressor loss