Tissue homeostasis requires controlled protein synthesis rates, and distinct cell types in healthy tissues exhibit different biosynthetic capabilities. In tumors, this regulation is disrupted by oncogenic alterations, many of which enhance the cell biosynthetic machinery, including ribosomal DNA transcription, ribosomal biogenesis, and protein production rates. We however discovered that the vast majority of ribosomal RNA and proteins synthesized in colorectal cancer (CRCs) are contributed by a limited subset of cells positioned immediately adjacent to the stroma. We showed that tumor cells that reside in these biosynthetic niches function as cancer stem cells although often they do not express LGR5 or other stem cell marker genes. In contrast, tumor cell differentiation is characterized by pervasive and permanent loss of biosynthetic capacities. To investigate the role of biosynthetic cells in CRC, we developed a methodology based on the use of CRISPR/Cas9 to edit the genomes of patient-derived organoids to introduce cell-specific ablation cassettes. Using this strategy in CRC models, we showed that lack of the biosynthetic cell compartment irreversibly halts tumor growth and induces tumor differentiation. We propose that zonation patterns of ribosomal DNA transcription and protein synthesis in CRC reflect the existence of a simple stem cell-like hierarchy based on the differential biosynthetic capacity of tumor cells. This model challenges some widely accepted views on the identity and features of stem cells in CRC and may inspire new therapeutic approaches.

Capturing energy from the environment (aka energy harvesting) is a very active area of research on account of its usefulness for powering sensors, devices in inaccessible locations, or just generally reducing our dependence on non-renewable energy sources. Two of the most common energy-harvesting mechanisms are photovoltaics, which convert sunlight into electricity, and electromechanics, which convert mechanical vibrations into electricity.  These two phenomena are based on, respectively, semiconducting junctions and piezoelectric insulators. Unfortunately, the different material families on which these phenomena are based complicate their integration into single devices.

This situation, however, has just changed with the discovery of a new effect, photoflexoelectricity, whereby photovoltaic semiconductor materials not only generate electricity when they vibrate, but the amount of electricity generated by the vibration multiplies by orders of magnitude under illumination. In a collaboration between several groups in China, the US and Catalonia, we have shown that halide perovskites, a family of highly efficient photovoltaic materials, display a photoflexoelectric effect whereby their bending-induced electricity is enhanced by light. We also show that photoflexoelectricity is not exclusive to halides but a general property of semiconductors. Photoflexoelectricity thus enables simultaneous electromechanical and photovoltaic energy harvesting in already commonly used photovoltaic materials and has the potential to revolutionize the field of energy harvesting.