Volume 26 Issue 5, May 2024

Two new landmark studies use innovative and complementary lineage tracing approaches in human cerebral organoids to reveal symmetric stem cell division and direct neurogenesis of basal radial glial cells to enable cortical growth, expansion and differentiation.

When transcription by RNA polymerase II is stalled by ultraviolet-induced DNA damage, it recruits repair factors, leading to excision of the damaged site and DNA synthesis to fill the gap. Three new studies show that, for aldehyde-induced DNA crosslinks, repair is activated by the same factors, but without base excision and gap filling.

We show that the mitochondrial fission proteins MiD49 and MiD51 are activated by fatty acyl-coenzyme A (FA-CoA). FA-CoA binds in a previously identified pocket located within MiDs, inducing their oligomerization and ability to activate the dynamin DRP1, ultimately promoting mitochondrial fission. Activated MiDs synergize with mitochondrial fission factor (MFF) in stimulating DRP1 activity, leading us to hypothesize that MiDs act upstream of MFF during mitochondrial fission.

Granath-Panelo and Kajimura review emerging evidence of mitochondrial heterogeneity in different contexts and discuss how mitochondrial malleability contributes to cell fate determination and tissue remodelling.

Metastatic colonization involves cancer-cell-intrinsic mechanisms and microenvironmental interactions, and a better understanding of the factors that influence the final, post-extravasation phases is crucial for therapeutically targeting metatstasis.

Coquand, Brunet Avalos et al. develop an imaging method to map basal radial glial cell division in human fetal tissue and cerebral organoids and detect abundant symmetric amplifying, but also direct neurogenic divisions bypassing intermediate progenitors.

Lindenhofer, Haendeler, Esk, Littleboy et al. perform whole-tissue lineage tracing in human cerebral organoids to reveal that a subpopulation of symmetrically dividing cells can adjust its lineage size depending on tissue demands.

Scarfò, Randolph et al. perform transcriptomic analysis of 28- to 32-day human embryos and identify CD32 as a marker of haemogenic endothelial cells (HECs), thus providing a strategy to isolate HECs from human embryos and pluripotent stem cell cultures.

Liu et al. find that long-chain acyl-coenzyme A activates two mitochondrial fission proteins, MiD49 and MiD51, by inducing their oligomerization. This activates their ability to stimulate DRP1 GTPase activity and triggers mitochondrial division.

Reicher, Reiniš et al. report a method for multicolour tagging using genome-scale intron-targeting sgRNA libraries that, in combination with computer vision, enables the systematic detection of protein localization changes.

Xu and colleagues identify a sequential palmitoylation–depalmitoylation mechanism that controls GSDMD cleavage by caspases, plasma membrane trafficking and oligomerization, thereby triggering pyroptosis in a spatial and temporal manner.

Three studies identify a transcription-coupled DNA–protein crosslink repair pathway that depends on the Cockayne syndrome proteins and the proteasome.

Three studies identify a transcription-coupled DNA–protein crosslink repair pathway that depends on the Cockayne syndrome proteins and the proteasome.

Three studies identify a transcription-coupled DNA–protein cross-link repair pathway that depends on the Cockayne syndrome proteins and the proteasome.

Chidley et al. report a CRISPR interference/activation screening platform to systematically interrogate the contribution of nutrient transporters to support cancer cell proliferation in environments of variable composition.