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Stem cells. Synthetic hydrogels support the expansion of viable human intestinal organoids from pluripotent stem cells and can be used as injectable vehicles for organoid engraftment and wound healing.p1326
Organoids are a powerful tool to study both physiological and disease processes. A completely synthetic matrix assembled from exchangeable modular parts has been developed and not only supports proliferation of human intestinal organoids derived from pluripotent embryonic stem cells, but also augments subsequent ad vivo implantation into injured murine colon.
PARP inhibitors (PARPi) kill BRCA1/2-mutated cancers, which become resistant when DNA repair functions are restored. Now, MUS81 nuclease inhibition due to EZH2 downregulation is found to restore DNA replication fork protection but not repair, leading to PARPi-resistance in mutant BRCA2 cells and patients. This challenges the DNA repair dominance in synthetic lethality.
A variety of non-coding RNAs have been reported as endogenous sponges for cancer-modulating miRNAs. However, miRNA trapping by transcripts with protein-coding functions is less understood. The mRNA of TYRP1 is now found to sequester the tumour suppressor miR-16 on non-canonical miRNA response elements in melanoma, thereby promoting malignant growth.
In the developing mouse pancreas, EGFR regulates apical polarity via PI(3)K and Rac1 and elicits different ligand-dependent effects: BTC enables β-cell commitment and EGF inhibits polarization of epithelial progenitors during the primary transition.
Cruz-Acuña et al. develop synthetic hydrogels that support the generation and expansion of viable human intestinal organoids from pluripotent stem cells and can be used as injectable vehicles for organoid engraftment and wound healing.
Boyd et al. monitored the effects of patient-derived acute myeloid leukaemia (AML) cells on human HSPCs in vivo and found that AML impairs bone marrow adipocyte differentiation, and this in turn impedes healthy endogenous haematopoiesis.
Gilot et al. have found that TYRP1 mRNA, in addition to coding for TYRP1 protein, can promote melanoma by sequestering the tumour suppressor miR-16, thus de-repressing the mRNA transcription of miR-16 target RAB17, which is involved in melanoma cell proliferation.
Liu et al. find that PKM2 methylated by CARM1 inhibits Ca2+ influx from endoplasmic reticulum to mitochondria, thus restraining mitochondrial oxidative phosphorylation while promoting aerobic glycolysis and breast cancer growth.
Rondinelli et al. show that EZH2-mediated H3K27me3 at stalled replication forks recruits MUS81 nuclease to facilitate fork degradation. Loss of EZH2 contributes to PARPi resistance in BRCA2-deficient tumours.
