Single-Cell Lineage Tracing Of Cancer Metastasis

The underpinnings of cancer metastasis remain poorly understood, in part due to a lack of tools for probing their emergence at high resolution. Here we present macsGESTALT, an inducible CRISPR-Cas9-based lineage recorder with highly efficient single-cell capture of both transcriptional and phylogenetic information. Applying macsGESTALT to a mouse model of metastatic pancreatic cancer, we recover ~380,000 CRISPR target sites and reconstruct dissemination of ~28,000 single cells across multiple metastatic sites. We find cells occupy a continuum of epithelial-to-mesenchymal transition (EMT) states. Metastatic potential peaks in rare, late-hybrid EMT states, which are aggressively selected from a predominately epithelial ancestral pool. The gene signatures of these late-hybrid EMT states are predictive of reduced survival in both human pancreatic and lung cancer patients, highlighting their relevance to clinical disease progression. Finally, we observe evidence for in vivo propagation of S100 family gene expression across clonally distinct metastatic subpopulations

Identifying functionally and topologically cohesive modules in protein interaction networks

Abstract unavailable please refer to PD

(Acido)bacterial diversity in space and time

Recent technological achievements enabled microbiologists to fully grasp the vast diversity of microbial life that is resident in soils, highly complex matrices of alternating micro-habitats on very small scales. Since then, microbial community composition has been catalogued for many different terrestrial habitats. This triggered the investigation and definition of processes which shape these communities. In most cases, the environment determines community composition, and similar habitats may feature similar microbial communities despite being far apart. However, some habitats have been described as subjected to pronounced neutral processes, which are dispersal, ecological drift or speciation. The balance between these process types is now the subject of many studies looking at microbial communities. It is also clear that these processes need to be monitored on both temporal and spatial scales, as the two dimensions are inseparably interlinked. However, most microbial studies deal with only one aspect, but do not control for the other. In this work, the outcome of a highly sophisticated plot scale experiment is presented encompassing 358 sampling locations distributed between six intra-annual sampling points on a 10 m x 10 m unfertilized grassland site in the Swabian Alb. RNA was extracted from the A-horizon of each soil and the hypervariable region 3 of the ribosomal small subunit was amplified and sequenced with barcoded Illumina sequencing. Roughly 400 million eubacterial reads were obtained. The dataset was used to assess the population dynamics of Acidobacteria, as well as the spatio-temporal co-occurenze of functionally depending microorganism. Additionally, preliminary results motivated the assessment of common methods for the examination of rhizospheric communities. In combination, the diversity of bacterial communities in space and time was tested from different angles, reflecting different research question, and they all revealed a far more complex reality than previously thought