Project description:During gestation, alveolar cells are derived from luminal progenitors in the mammary gland. However, the mechanism underlying luminal progenitor commitment to alveolar cells remains largely unknown. By using five genetically modified mouse lines and single cell RNA sequencing, we identified a Kindlin-2 - Stat3 - Dll1 signaling cascade in myoepithelial cells which controls the inactivation of Notch signaling in luminal cells that consequently drives luminal progenitor commitment to alveolar cells. We found that loss of Kindlin-2 in myoepithelial cells impairs mammary morphogenesis and alveologenesis, and lactation. Single-cell profiling reveals that Kindlin-2 loss significantly decreases the proportion of alveolar cells.
Project description:Kindlin-2, an integrin-interacting FERM-domain-containing protein, has been known to play critical roles for tumor progression. However, the role of Kindlin-2 in renal cell carcinoma (RCC) progression has not been reported. We aim to investigate the role of Kindlin-2 in the progression of RCC and the underlying mechanisms. To uncover the related pathway in which Kindlin-2 is involved to promote clear cell renal cell carcinoma progression, ACHN control and Kindlin-2-depleting cells were analyzed by Affymetrix GeneChip human Gene 1.0 ST Arrays. ACHN cells were transfected with control short hairpin RNA (shRNA) or Kindlin-2 shRNA. ACHN control and Kindlin-2-depleting cells cDNAs were hybridized to Affymetrix GeneChip Human Gene 1.0 ST arrays. Data were analyzed by Expression Console 1.4.1.
Project description:According to the Canadian Food Inspection Agency and Health Canada, genetically modified crops are considered safe if they are substantially equivalent to a conventional crop in regards to agronomic, physiological and compositional characteristics. A recurring issue in safety assessment of genetically modified crops is the paucity of analytical methods to detect unintended or unexpected outcomes of genetic modification. Traditional targeted compound comparative analyses are limited in scope and capacity to detect unintended changes in chemical composition. This study explored the potential of using microarray technology to assess the substantial equivalence of gene expression profiles between genetically modified and conventional soybean cultivars. Different pre processing methods were applied to the raw expression data from the arrays, and clustering methods were used to try and differentiate the genetically modified cultivars from the conventional cultivars. Results showed that more variation existed between different strains of conventional cultivars than between conventional and genetically modified cultivars. For more information, please see: Cheng, K.C., Beaulieu, J., Iquira, E., Belzile, F.J., Fortin, M.G. and Strömvik, M.V. (2008). âEffect of transgenes on global gene expression in soybean is within the natural range of variation of their conventional counterparts.â Journal of Agricultural and Food Chemistry (in press) Experiment Overall Design: Five samples (biological replicates) of total RNA from each of the five different soybean varieties were selected for hybridization to Affymetrix Soybean GeneChips, for a total of 25 chips (following total RNA integrity assessment). Spike controls B2, bio-B, bio-C, bio-D and Cre-x were added to each hybridization cocktail. Arrays were washed and stained in an Affymetrix Fluidics Station prior to scanning on the Affymetrix GeneChip Scanner 3000. Image acquisition and processing was done with the Affymetrix Microarray Analysis Suite 5.0.
Project description:According to the Canadian Food Inspection Agency and Health Canada, genetically modified crops are considered safe if they are substantially equivalent to a conventional crop in regards to agronomic, physiological and compositional characteristics. A recurring issue in safety assessment of genetically modified crops is the paucity of analytical methods to detect unintended or unexpected outcomes of genetic modification. Traditional targeted compound comparative analyses are limited in scope and capacity to detect unintended changes in chemical composition. This study explored the potential of using microarray technology to assess the substantial equivalence of gene expression profiles between genetically modified and conventional soybean cultivars. Different pre processing methods were applied to the raw expression data from the arrays, and clustering methods were used to try and differentiate the genetically modified cultivars from the conventional cultivars. Results showed that more variation existed between different strains of conventional cultivars than between conventional and genetically modified cultivars. For more information, please see: Cheng, K.C., Beaulieu, J., Iquira, E., Belzile, F.J., Fortin, M.G. and Strömvik, M.V. (2008). Effect of transgenes on global gene expression in soybean is within the natural range of variation of their conventional counterparts. Journal of Agricultural and Food Chemistry. Keywords: Expression comparison between genetically modified cultivars
Project description:Kindlin-2, an integrin-interacting FERM-domain-containing protein, has been known to play critical roles for tumor progression. However, the role of Kindlin-2 in renal cell carcinoma (RCC) progression has not been reported. We aim to investigate the role of Kindlin-2 in the progression of RCC and the underlying mechanisms. To uncover the related pathway in which Kindlin-2 is involved to promote clear cell renal cell carcinoma progression, ACHN control and Kindlin-2-depleting cells were analyzed by Affymetrix GeneChip human Gene 1.0 ST Arrays.
Project description:Kindler syndrome (KS) is a rare genodermatosis resulting from loss-of-function mutations in FERMT1, the gene that encodes Kindlin-1. KS patients have a high propensity to develop aggressive and metastatic cutaneous squamous cell carcinoma (SCC). In this study, we show that loss of Kindlin-1 in a mouse model of cutaneous SCC leads to increased migration, invasion and degradation of collagen. Loss of Kindlin-1 increased tumor growth in vivo and in 3D spheroids, which was associated with the development of a hypoxic tumor environment and increased glycolysis. One of the most highly upregulated genes in Kindlin-1-depleted tumors was Mmp13, and the increased expression of MMP13 was responsible for driving the increased migration and invasion of the Kindlin-1-depleted SCC cells. These results provide evidence that Kindlin-1 loss in SCC can promote migration and invasion through the upregulation of MMP13, and offer novel insights into how Kindlin-1 loss leads to the development of a hypoxic environment that is permissive for tumor growth.
Project description:To explore the mechanism of Kindlin-2 regulating invasion and metastasis of human Hepatocellular carcinoma, we performed gene expression microarray analysis on Kindlin-2 knockdown LM3 cells and the control cells to compare the gene expression levels between the two groups.
Project description:To investigation the role of PTH and Kindlin-2 in bone development, we performed single-cell RNA-sequencing. From Con-veh, Con-PTH, cKO-veh, cKO-PTH, we profiled more than 20k single cells, including multi-potent mesenchymal stromal cells (MSC), osteoprogenitors, osteoblasts, chondrocytes, fibroblasts, endothelial cells, smooth muscle cells, skeletal muscle cells, pericytes, and schwann cells. We found proportion of part of these cells were significant altered by PTH or Kindlin-2 loss, especially for MSC, osteoblast, chondrocyte, and fibroblast. Transcriptomic analysis revealed gene expression was dramatically regulated by PTH or Kindlin-2 loss.