Volume 23 Issue 11, November 2021

How lymphatic vessels arise from veins is still poorly understood. A study reports the discovery of a ribosome biogenesis regulator Ddx21 as a previously unappreciated specific factor that is important for the first steps of lymphatic but not blood vessel development. The finding may lead to better strategies to selectively target lymphangiogenesis.

The WAVE regulatory complex is well known as an orchestrator of actin dynamics at the leading edge of migrating cells. A recent study shows how mechanical effects can regulate the WAVE complex and explains the importance of forces generated by actin filaments to control new actin generation at the leading edge.

During the repair of DNA breaks by homologous recombination, damaged DNA seeks out intact, similar in sequence segments to use as a template. In this issue, Piazza, Bordelet and colleagues describe three-dimensional chromosome architecture remodelling during homologous recombination and show that cohesin restricts homology search in cis, independently of sister chromatid cohesion.

FGFR-altered triple negative breast cancer (TNBC) develops adaptive resistance to FGFR inhibitor therapy. A new study shows that sustained FGFR inhibition causes SWI/SNF complex eviction at YAP-recruited enhancers followed by increased mTORC1 activity. Dual inhibition of YAP or mTORC1 and FGFR has a synergistic effect on tumour growth.

In this Perspective, Börner et al. discuss initiatives by 16 consortia to construct a Human Reference Atlas (HRA) comprising reference organs linked to tables that name major anatomical structures, cell types, plus biomarkers (ASCT+B) and present examples of HRA usage.

In this Perspective, Teichmann and colleagues present ongoing efforts from consortia of the Human Cell Atlas to harmonize and integrate data sources into a reference cell ontology and the contributions of cell ontologies to discovery.

Hogan and colleagues report that the RNA helicase Ddx21 mediates Vegfc-stimulated lymphangiogenesis during zebrafish development through controlling rDNA transcription and ribosome biogenesis in endothelial cells.

Mehidi et al. show that piconewton forces exerted by the polymerization of individual actin filaments displace the WAVE regulatory complex from lamellipodial tips, thereby regulating WAVE complex activity during cell migration.

Gasser and colleagues report that H3K9me2 and H3K9me3 repress lineage-specific and germline genes by restricting the activity of a subset of transcription factors in terminally differentiated Caenorhabditis elegans tissues.

Piazza et al. report that following double-strand break (DSB) formation in S. cerevisiae, cohesin at DSBs facilitates local homology search during repair by homologous recombination, while suppressing DSB contacts with genome-wide double-strand DNAs.

Li et al. define an adaptive resistance mechanism against FGFR inhibitor treatment in breast cancer attributed to loss of BRG1 chromatin recruitment, reactivation of YAP-dependent enhancers and upregulation of amino acid-induced mTORC1 activity.

Frede et al. perform single-cell transcriptome and chromatin accessibility profiling of immune cells isolated from patients with refractory multiple myeloma before or during the course of chemotherapy.