It is estimated that only 0.02% of disseminated tumour cells are able to seed overt metastases. While this suggests the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unclear.
View Article and Find Full Text PDFThe tumour evolution model posits that malignant transformation is preceded by randomly distributed driver mutations in cancer genes, which cause clonal expansions in phenotypically normal tissues. Although clonal expansions can remodel entire tissues, the mechanisms that result in only a small number of clones transforming into malignant tumours remain unknown. Here we develop an in vivo single-cell CRISPR strategy to systematically investigate tissue-wide clonal dynamics of the 150 most frequently mutated squamous cell carcinoma genes.
View Article and Find Full Text PDFBacteria use CRISPR Cas systems to defend against invading foreign nucleic acids, e.g., phage genomes, plasmids or mobile genetic elements.
View Article and Find Full Text PDFSequencing-based spatial transcriptomics (ST) methods allow unbiased capturing of RNA molecules at barcoded spots, charting the distribution and localization of cell types and transcripts across a tissue. While the coarse resolution of these techniques is considered a disadvantage, we argue that the inherent proximity of transcriptomes captured on spots can be leveraged to reconstruct cellular networks. To this end, we developed ISCHIA (Identifying Spatial Co-occurrence in Healthy and InflAmed tissues), a computational framework to analyze the spatial co-occurrence of cell types and transcript species within spots.
View Article and Find Full Text PDFAdult neural stem cells (NSCs) contribute to lifelong brain plasticity. In the adult mouse ventricular-subventricular zone, NSCs are heterogeneous and, depending on their location in the niche, give rise to different subtypes of olfactory bulb (OB) interneurons. Here, we show that multiple regionally distinct NSCs, including domains that are usually quiescent, are recruited on different gestation days during pregnancy.
View Article and Find Full Text PDFInducible gene expression is useful for biotechnological applications and for studying gene regulation and function in bacteria. Many inducible systems that perform in model organisms such as the Gammaproteobacterium do not perform well in other bacteria that are of biotechnological interest. Typical problems include weak or leaky expression.
View Article and Find Full Text PDFIn , the methionine biosynthesis genes and are preceded by S-adenosyl-L-methionine (SAM) riboswitches of the SAM-II class. Upon SAM binding, structural changes in the riboswitch were predicted to cause transcriptional termination, generating the sRNA RZ. By contrast, the riboswitch was predicted to regulate translation from an AUG1 codon.
View Article and Find Full Text PDFTemperature above the physiological optimum is a stress condition frequently faced by bacteria in their natural environments. Here, we were interested in the correlation between levels of RNA and protein under heat stress. Changes in RNA and protein levels were documented in cultures of Rhodobacter sphaeroides using RNA sequencing, quantitative mass spectrometry, western blot analysis, in vivo [ S] methionine-labelling and plasmid-borne reporter fusions.
View Article and Find Full Text PDFTight control of cell division is essential for survival of most organisms. For prokaryotes, the regulatory mechanisms involved in the control of cell division are mostly unknown. We show that the small non-coding sRNA StsR has an important role in controlling cell division and growth in the alpha-proteobacterium Rhodobacter sphaeroides.
View Article and Find Full Text PDFBiospektrum (Heidelb)
October 2020