Project description:At the cellular level, the malignant characteristics of GBM are largely attributed to GBM stem cells (GSCs). These cells, endowed with stem-like properties, can self-renew, generate diverse cancerous cell populations, and initiate tumors in vivo. The GSC lines, NCH644 and NCH421k, when cultured as neurospheres (NS) — a condition that preserves their stem-like state, as evidenced by the expression of stem cell markers like SOX2, CD133, and Nestin — were found to align with the PN subclass and CL-B/C respectively.
Project description:Phenotypic plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced phenotypic plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies, including GRO-seq on enhancer landscapes, demonstrate that the global enhancer gain/loss reprogramming driven by the differential interactions between ER-alpha and other oncogenic transcription factors (TFs), predominantly GATA3 and AP1, profoundly alters breast cancer transcriptional programs. Our functional studies in multiple biological systems support a coordinate role of GATA3 and AP1 in enhancer reprogramming that drives phenotypic plasticity to achieve endocrine resistance or cancer invasive progression. Thus, changes in TF-TF and TF-enhancer interactions can lead to genome-wide enhancer reprogramming, resulting in transcriptional dysregulations that promote plasticity and cancer therapy-resistance progression
Project description:Traditionally, the study of evolution has focused on heritable variation, because selection on non-heritable phenotypic variation was deemed non-important for its inability to cause evolutionary responses such as diversification of lineages. Recently however, it has been suggested that also environmentally induced phenotypic variation such as phenotypic plasticity can play an important role in adaptive responses resulting in diversification. The purpose of this study is to investigate the importance of phenotypic plasticity for the diversification of lineages, using life history, morphological traits, and genomic profiling during post embryonic development in plastic and non-plastic genotypes of the common frog Rana temporaria. Six animals each originating from four different islands were reared in either constant or reduced water conditions and hepatic mRNA levels of Gosner stage 37 animals evaluated by MAGEX DNA array analysis.
Project description:Triple negative breast cancer (TNBC) is the most lethal breast cancer subgroup, as lack of targeted therapies and drug resistance reduce survival rates. Cellular plasticity enables cells to adapt non-genetically and overcome therapeutic pressure, thereby embodying a critical clinical hurdle. The epithelial-mesenchymal transition (EMT) is an example of phenotypic reprogramming linked to plasticity, drug resistance and metastasis. However, its exact impact on population diversity under therapeutic pressure is unknown. Here, we used single cell transcriptomics to investigate phenotypic diversity dynamics upon drug treatment in two human in vitro models of TNBC plasticity.
Project description:Triple negative breast cancer (TNBC) is the most lethal breast cancer subgroup, as lack of targeted therapies and drug resistance reduce survival rates. Cellular plasticity enables cells to adapt non-genetically and overcome therapeutic pressure, thereby embodying a critical clinical hurdle. The epithelial-mesenchymal transition (EMT) is an example of phenotypic reprogramming linked to plasticity, drug resistance and metastasis. However, its exact impact on population diversity under therapeutic pressure is unknown. Here, we used single cell transcriptomics to investigate phenotypic diversity dynamics upon drug treatment in two human in vitro models of TNBC plasticity.
Project description:Traditionally, the study of evolution has focused on heritable variation, because selection on non-heritable phenotypic variation was deemed non-important for its inability to cause evolutionary responses such as diversification of lineages. Recently however, it has been suggested that also environmentally induced phenotypic variation such as phenotypic plasticity can play an important role in adaptive responses resulting in diversification. The purpose of this study is to investigate the importance of phenotypic plasticity for the diversification of lineages, using life history, morphological traits, and genomic profiling during post embryonic development in plastic and non-plastic genotypes of the common frog Rana temporaria.