Volume 22 Issue 3, March 2020

The lack of endogenous reporter lines is a bottleneck in the study of subcellular dynamics in human adult stem cell (ASC)-derived organoids. An approach using CRISPR–Cas9-mediated homology-independent organoid transgenesis (CRISPR–HOT) in ASC-derived organoids now narrows the gap between basic research and translational studies in human organoids.

Misfolded proteins in the endoplasmic reticulum (ER) are returned to the cytosol and destroyed by a process known as ER-associated degradation (ERAD). Hrd1 has been implicated as the channel that mediates the transport of ERAD substrates to the cytosol. A study demonstrates that Hrd1 is gated by autoubiquitination and a soluble ERAD substrate.

Lau et al. quantify endogenous concentrations of the chemokine Cxcl12 and its binding affinity for its cognate receptor Cxcr4 in zebrafish embryos, uncovering a negative-feedback loop governing directional cell migration in vivo.

Ubiquitin ligase Hrd1 is essential for endoplasmic-reticulum-associated protein degradation. Vasic et al. demonstrate that Hrd1 forms a retrotranslocation channel controlled by auto-ubiquitination and substrate binding.

Li et al. demonstrate the efficacy of correcting the mutated TERT promoter using a programmable base editing, highlighting its ability to induce senescence, arrest and regression in brain tumour models.

Montagner et al. show that lung epithelial cells induce Sfrp2 expression and fibronectin fibril formation in disseminated breast cancer cells, thereby promoting their survival and latency in the lung.

Zheng et al. discover a type of perinuclear microtubule-organizing center, which is assembled by multiple factors and regulates retrograde endosomal trafficking and plasma membrane growth.

Davis et al. demonstrate heterogeneous and distinct transcriptome programs in breast cancer micrometastasis associated with upregulated mitochondrial oxidative phosphorylation.

Artegiani, Hendriks et al. describe a CRISPR–Cas9-based method to efficiently generate human knock-in organoids using non-homologous end joining to study rare intestinal cell types and human hepatocyte division.

Yue, Zong, Li, Li, Zhang, Wu et al. introduce an in toto live-imaging system to track cardiac ventricle chamber formation at single-cell resolution for up to 1.5 days and digitally reconstruct cell dynamics.

Kim et al. develop an optogenetic visualization approach that can rapidly and reversibly trap messenger RNA molecules in protein clusters, thereby restricting their access to ribosomes and dampening translation efficiency.