High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer.

Charting the spatiotemporal dynamics of cell fate determination in development and disease is a long-standing objective in biology. Here we present the design, development, and extensive validation of PEtracer, a prime editing-based, evolving lineage tracing technology compatible with both single-cell sequencing and multimodal imaging methodologies to jointly profile cell state and lineage in dissociated cells or while preserving cellular context in tissues with high spatial resolution. Using PEtracer coupled with MERFISH spatial transcriptomic profiling in a syngeneic mouse model of tumor metastasis, we reconstruct the growth of individually-seeded tumors in vivo and uncover distinct modules of cell-intrinsic and cell-extrinsic factors that coordinate tumor growth.

High-resolution spatial mapping of cell state and lineage dynamics with PEtracer.

Charting the spatiotemporal dynamics of cell fate determination in development and disease is a long-standing objective in biology. Here we present the design, development, and extensive validation of PEtracer, a prime editing-based, evolving lineage tracing technology compatible with both single-cell sequencing and multimodal imaging methodologies to jointly profile cell state and lineage in dissociated cells or while preserving cellular context in tissues with high spatial resolution. Using PEtracer coupled with MERFISH spatial transcriptomic profiling in a syngeneic mouse model of tumor metastasis, we reconstruct the growth of individually-seeded tumors and uncover distinct modules of cell-intrinsic and cell-extrinsic factors that coordinate tumor growth.

Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis.

Tumor progression is driven by dynamic interactions between cancer cells and their surrounding microenvironment. Investigating the spatiotemporal evolution of tumors can provide crucial insights into how intrinsic changes within cancer cells and extrinsic alterations in the microenvironment cooperate to drive different stages of tumor progression. Here, we integrate high-resolution spatial transcriptomics and evolving lineage tracing technologies to elucidate how tumor expansion, plasticity, and metastasis co-evolve with microenvironmental remodeling in a -driven mouse model of lung adenocarcinoma.

Accelerating Ice Loss From Peripheral Glaciers in North Greenland.

In recent decades, Greenland's peripheral glaciers have experienced large-scale mass loss, resulting in a substantial contribution to sea level rise. While their total area of Greenland ice cover is relatively small (4%), their mass loss is disproportionally large compared to the Greenland ice sheet. Satellite altimetry from Ice, Cloud, and land Elevation Satellite (ICESat) and ICESat-2 shows that mass loss from Greenland's peripheral glaciers increased from 27.

Greenland Mass Trends From Airborne and Satellite Altimetry During 2011-2020.

We use satellite and airborne altimetry to estimate annual mass changes of the Greenland Ice Sheet. We estimate ice loss corresponding to a sea-level rise of 6.9 ± 0.

Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer.

Despite advances in precision medicine, the clinical prospects for patients with ovarian and uterine cancers have not substantially improved. Here, we analyzed genome-scale CRISPR-Cas9 loss-of-function screens across 851 human cancer cell lines and found that frequent overexpression of SLC34A2-encoding a phosphate importer-is correlated with sensitivity to loss of the phosphate exporter XPR1, both in vitro and in vivo. In patient-derived tumor samples, we observed frequent PAX8-dependent overexpression of SLC34A2, XPR1 copy number amplifications and XPR1 messenger RNA overexpression.

High-Resolution Tritium Profile in an Ice Core from Camp Century, Greenland.

We measure H in an ice core from Camp Century. The temporal distribution of H concentration in the ice core corresponds generally well with the historical record of explosive yields of atmospheric nuclear weapons tests. Maximum H values observed in 1962-1963 are comparable to those in ice core or precipitation in many other locations in the Northern Hemisphere.

Vulnerability of the North Water ecosystem to climate change.

High Arctic ecosystems and Indigenous livelihoods are tightly linked and exposed to climate change, yet assessing their sensitivity requires a long-term perspective. Here, we assess the vulnerability of the North Water polynya, a unique seaice ecosystem that sustains the world's northernmost Inuit communities and several keystone Arctic species. We reconstruct mid-to-late Holocene changes in sea ice, marine primary production, and little auk colony dynamics through multi-proxy analysis of marine and lake sediment cores.

A first constraint on basal melt-water production of the Greenland ice sheet.

The Greenland ice sheet has been one of the largest sources of sea-level rise since the early 2000s. However, basal melt has not been included explicitly in assessments of ice-sheet mass loss so far. Here, we present the first estimate of the total and regional basal melt produced by the ice sheet and the recent change in basal melt through time.

Cyclin-dependent Kinase 1 and Aurora Kinase choreograph mitotic storage and redistribution of a growth factor receptor.

Endosomal trafficking of receptors and associated proteins plays a critical role in signal processing. Until recently, it was thought that trafficking was shut down during cell division. Thus, remarkably, the regulation of trafficking during division remains poorly characterized.

Centennial response of Greenland's three largest outlet glaciers.

The Greenland Ice Sheet is the largest land ice contributor to sea level rise. This will continue in the future but at an uncertain rate and observational estimates are limited to the last few decades. Understanding the long-term glacier response to external forcing is key to improving projections.

Multiplexed single-cell transcriptional response profiling to define cancer vulnerabilities and therapeutic mechanism of action.

Assays to study cancer cell responses to pharmacologic or genetic perturbations are typically restricted to using simple phenotypic readouts such as proliferation rate. Information-rich assays, such as gene-expression profiling, have generally not permitted efficient profiling of a given perturbation across multiple cellular contexts. Here, we develop MIX-Seq, a method for multiplexed transcriptional profiling of post-perturbation responses across a mixture of samples with single-cell resolution, using SNP-based computational demultiplexing of single-cell RNA-sequencing data.

Inferring Tunicate Relationships and the Evolution of the Tunicate Hox Cluster with the Genome of Corella inflata.

Tunicates, the closest living relatives of vertebrates, have served as a foundational model of early embryonic development for decades. Comparative studies of tunicate phylogeny and genome evolution provide a critical framework for analyzing chordate diversification and the emergence of vertebrates. Toward this goal, we sequenced the genome of Corella inflata (Ascidiacea, Phlebobranchia), so named for the capacity to brood self-fertilized embryos in a modified, "inflated" atrial chamber.

Variable levels of drift in tunicate cardiopharyngeal gene regulatory elements.

Background: Mutations in gene regulatory networks often lead to genetic divergence without impacting gene expression or developmental patterning. The rules governing this process of developmental systems drift, including the variable impact of selective constraints on different nodes in a gene regulatory network, remain poorly delineated.

Results: Here we examine developmental systems drift within the cardiopharyngeal gene regulatory networks of two tunicate species, and Cross-species analysis of regulatory elements suggests that -regulatory architecture is largely conserved between these highly divergent species.

A synthesis of the basal thermal state of the Greenland Ice Sheet.

The basal thermal state of an ice sheet (frozen or thawed) is an important control upon its evolution, dynamics and response to external forcings. However, this state can only be observed directly within sparse boreholes or inferred conclusively from the presence of subglacial lakes. Here we synthesize spatially extensive inferences of the basal thermal state of the Greenland Ice Sheet to better constrain this state.

Holocene deceleration of the Greenland Ice Sheet.

Recent peripheral thinning of the Greenland Ice Sheet is partly offset by interior thickening and is overprinted on its poorly constrained Holocene evolution. On the basis of the ice sheet's radiostratigraphy, ice flow in its interior is slower now than the average speed over the past nine millennia. Generally higher Holocene accumulation rates relative to modern estimates can only partially explain this millennial-scale deceleration.

Spatial and temporal distribution of mass loss from the Greenland Ice Sheet since AD 1900.

The response of the Greenland Ice Sheet (GIS) to changes in temperature during the twentieth century remains contentious, largely owing to difficulties in estimating the spatial and temporal distribution of ice mass changes before 1992, when Greenland-wide observations first became available. The only previous estimates of change during the twentieth century are based on empirical modelling and energy balance modelling. Consequently, no observation-based estimates of the contribution from the GIS to the global-mean sea level budget before 1990 are included in the Fifth Assessment Report of the Intergovernmental Panel on Climate Change.

Considering thermal-viscous collapse of the Greenland ice sheet.

We explore potential changes in Greenland ice sheet form and flow associated with increasing ice temperatures and relaxing effective ice viscosities. We define "thermal-viscous collapse" as a transition from the polythermal ice sheet temperature distribution characteristic of the Holocene to temperate ice at the pressure melting point and associated lower viscosities. The conceptual model of thermal-viscous collapse we present is dependent on: (1) sufficient energy available in future meltwater runoff, (2) routing of meltwater to the bed of the ice sheet interior, and (3) efficient energy transfer from meltwater to the ice.