Basic helix-loop-helix transcription factor Twist1 is a master regulator of Epithelial-Mesenchymal Transition (EMT), a cellular program implicated in different stages of development as well as metastatic dissemination of carcinomas. Here, we show that Twist1 requires TGF-beta type-I receptor (TGFBR1)-activation to bind an enhancer region of downstream effector ZEB1, thereby inducing ZEB1 transcription and EMT. When TGFBR1-phosphorylation is inhibited, Twist1 generates a distinct cell state characterized by collective invasion, simultaneous proliferation and expression of endothelial markers.
View Article and Find Full Text PDFWe present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis.
View Article and Find Full Text PDFMaster regulators of the epithelial-mesenchymal transition such as Twist1 and Snail1 have been implicated in invasiveness and the generation of cancer stem cells, but their persistent activity inhibits stem-cell-like properties and the outgrowth of disseminated cancer cells into macroscopic metastases. Here, we show that Twist1 activation primes a subset of mammary epithelial cells for stem-cell-like properties, which only emerge and stably persist following Twist1 deactivation. Consequently, when cells undergo a mesenchymal-epithelial transition (MET), they do not return to their original epithelial cell state, evidenced by acquisition of invasive growth behavior and a distinct gene expression profile.
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July 2012
Redirected walking techniques allow people to walk in a larger virtual space than the physical extents of the laboratory. We describe two experiments conducted to investigate human sensitivity to walking on a curved path and to validate a new redirected walking technique. In a psychophysical experiment, we found that sensitivity to walking on a curved path was significantly lower for slower walking speeds (radius of 10 m versus 22 m).
View Article and Find Full Text PDFThe aim of this work is to increase the effectiveness of real world medical training simulations by helping trainees gain a better understanding of the importance of communication and teamwork. Therefore we develop an online application which can be used together with real world simulations to improve training. To produce the online application we reconstructed two real world scenarios (one with students and one with practitioners) in an immersive virtual environment.
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