Megabase-scale human genome rearrangement with programmable bridge recombinases

Researchers explored whether bridge recombinases — naturally occurring RNA-guided enzymes capable of rearranging DNA — could be adapted to edit the human genome at large scales. They identified and engineered a new variant called ISCro4, using rational redesign of its guide RNA alongside deep mutational scanning of the recombinase protein itself to optimize performance. The approach achieved insertion efficiencies of up to 20% in human cells and genome-wide specificity reaching 82%. Beyond insertions, the system could flip or remove chromosomal segments as large as 0.93 megabases. The researchers also demonstrated that plasmid-delivered versions of the tool could excise disease-relevant regulatory regions and problematic repeat expansions. These results establish bridge recombinases as a programmable platform for large-scale genomic rearrangements in human cells, with potential therapeutic relevance for conditions caused by structural genomic variants or pathological repeat sequences.

Read the original article →

Rapid evolution predicts demographic recovery after extreme drought

During severe drought conditions, declining populations may survive by evolving rapidly enough to keep pace with environmental stress — a concept called evolutionary rescue. While this has been shown in lab settings and computer models, evidence from wild populations under real climate pressure has been scarce. Researchers studied the scarlet monkeyflower (*Mimulus cardinalis*) across 55 populations during an exceptional drought, using whole-genome sequencing to pinpoint genetic variants associated with climate adaptation. By simultaneously monitoring population sizes and shifts in allele frequencies, they found widespread population decline during the drought, followed by variable recovery. Crucially, recovery was predictable from standing genetic variation and rapid evolutionary change at climate-associated loci — but not at neutral loci. This distinction confirms that adaptive rather than random genetic variation drives demographic rebound, providing rare empirical evidence that evolutionary rescue can occur in wild populations facing climate change.

Read the original article →

Whole-embryo spatial transcriptomics at subcellular resolution from gastrulation to organogenesis

Researchers developed a technique called weMERFISH to map gene activity across entire zebrafish embryos with subcellular precision during early development. By profiling 495 genes spatially and building an online atlas covering nearly 26,000 genes and roughly 295,000 chromatin accessibility regions across embryogenesis, they uncovered how gene expression patterns are shaped by tissue-specific regulatory elements and linked to cell maturation and morphogenesis. Combining this spatial data with live imaging, they found that visually similar expression patterns can arise through distinct temporal dynamics, and that sharp boundaries between cell populations form primarily through changes in gene expression rather than physical cell sorting. The work provides a powerful framework for systematically dissecting the regulatory logic of embryonic development at high resolution.

Read the original article →

High-throughput single-cell omics using semipermeable capsules

Researchers developed semipermeable capsules (SPCs) as a flexible platform for profiling individual cells at scale. Unlike conventional droplet microfluidics, which cannot maintain cells for extended periods, SPCs are biocompatible enough to support single-cell culture and clonal expansion over long timeframes. The capsules are compatible with multiple nucleic acid workflows, including single-cell genome sequencing, mRNA sequencing, and FACS-based isolation of individual transcriptomes using nucleic acid markers. Because the capsules are permeable, they allow reagents to diffuse in and out while keeping cellular contents contained, enabling multistep biochemical reactions without transferring cells between compartments. The technology is designed to be scalable and customizable, making it broadly useful for high-throughput single-cell omics. By addressing a key drawback of droplet-based systems—the inability to maintain live cells long-term—SPCs expand what is experimentally achievable in studies of cellular heterogeneity and complexity.

Read the original article →

Evolutionary adaptation to global change reduces sustainable fisheries yields

Fish populations are expected to adapt genetically to warming oceans, but most climate impact forecasts for fisheries ignore this possibility. Researchers built a model combining climate projections with evolutionary dynamics to predict how fish life histories will shift under future warming. The model forecasts that fish in warmer waters will grow faster yet evolve to reach sexual maturity earlier, ultimately reducing their maximum body size. While this evolutionary shift helps fish maintain fitness under changed conditions, it hurts fisheries: yields could decline roughly 50% more than climate-only models would suggest. This bias toward optimism holds across all emissions scenarios but is most pronounced under the most severe ones. The findings highlight a critical blind spot — ignoring evolutionary responses systematically overestimates how much fish populations can sustainably produce, with significant implications for global food security planning and fisheries management under climate change.

Read the original article →

Lifelong behavioral screen reveals an architecture of vertebrate aging

Researchers continuously tracked the behavior of individual African killifish at high resolution from adolescence until natural death, building one of the most complete pictures of vertebrate aging yet assembled. They discovered that animals age along distinct individual trajectories, with long-lived fish displaying measurably different behavior from short-lived ones even relatively early in life — differences tied to organ-specific changes in gene expression. Machine-learning models trained on this data could accurately estimate an animal's current age and, strikingly, predict its future lifespan from behavioral data collected at a young age alone. The work also revealed that aging does not unfold gradually and continuously; instead, animals pass through a series of stable behavioral stages separated by sharp transitions. These findings suggest vertebrate aging has an underlying architecture that is structured, predictable, and detectable in behavior long before death.

Read the original article →

Multistep genomics on single cells and live cultures in subnanoliter capsules

Researchers developed a new platform called capsules with amphiphilic gel envelopes (CAGEs) to address a key limitation in single-cell genomics: most multi-step functional assays, especially those involving living cells, cannot yet be run at high throughput. CAGEs are subnanoliter compartments whose gel walls selectively retain cells and large molecules while allowing small reagents, enzymes, and growth media to pass freely in and out. This design lets researchers culture cells inside the capsules and then perform genomic readouts on the same cells. The team built barcoding strategies for CAGE-derived DNA libraries and used them to capture transcriptomes from tens of thousands of expanding clonal populations, enabling measurement of how gene expression programs persist over cell divisions. Because CAGEs are compatible with a wide range of enzymatic reactions, the approach could broadly extend high-throughput single-cell methods to live-cell experimental settings.

Read the original article →