Biology subjects

Ruan, Y.

Publications and source records attributed to Ruan, Y..

58 records · Page 4Linked to original sources

bioRxiv2018

Multiplex Chromatin Interaction Analysis with Single-Molecule Precision

We describe a microfluidics-based strategy for genome-wide analysis of multiplex chromatin interactions with single-molecule precision. In multiplex chromatin interaction analysis (multi-ChIA), individual chromatin complexes are partitioned into droplets that contain a gel bead with unique DNA barcode, in which tethered chromatin DNA fragments are barcoded and amplified for sequencing and mapping to demarcate chromatin contacts. Thus, multi-ChIA has the unprecedented ability to uncover multiplex chromatin interactions at single-molecule level, which has been impossible using previous methods that rely on analyzing pairwise contacts via proximity ligation. We demonstrate that multiplex chromatin interactions predominantly contribute to topologically associated domains, and clusters of gene promoters and enhancers provide a fundamental topological framework for co-transcriptional regulation.

genomics↗

bioRxiv2018

Observing the Cell in Its Native State: Imaging Subcellular Dynamics in Multicellular Organisms

True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution without inducing undue stress on either. We combined lattice light sheet microscopy with two-channel adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages, and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.\n\nOne Sentence SummaryCombining lattice light sheet microscopy with adaptive optics enables high speed, high resolution in vivo 3D imaging of dynamic processes inside cells under physiological conditions within their parent organisms.

cell biology↗

bioRxiv2018

Electron transfer dictates metabolic reprogramming in proliferating cells under hypoxia

Metabolic reprogramming extensively occurs in proliferating cancer cells. This phenomenon occurs highly heterogeneously, but its origin has remained unclear. Here we use a physicochemical concept of free electron potential (FEP) and its equation of state to profile metabolites. We demonstrate that FEP change between substrates and products exactly reflects electrons dissipated in a metabolic transformation. Based on the law of conservation of electron in chemical reactions, a function of FEP change for central metabolism in proliferating cells are further derived, and it can accurately predict metabolic behaviors under hypoxia by maximizing the cellular FEP change to consume electrons. Therefore, enabling electron transfer dictates metabolic reprogramming in hypoxic cells, which underlies the major findings in cancer metabolism and is supported by our experiments. Importantly, our model established on FEP helps to reveal a combination of promising targets to inhibit tumor growth under hypoxia by blocking electron consumption, and could also guide future studies on cancer metabolism under hypoxia.

biochemistry↗

bioRxiv2017

The Tandem Duplicator Phenotype is a prevalent genome-wide cancer configuration driven by distinct gene mutations

The tandem duplicator phenotype (TDP) is a genome-wide instability configuration primarily observed in breast, ovarian and endometrial carcinomas. Here, we stratify TDP tumors by classifying their tandem duplications (TDs) into three span intervals, with modal values of 11 Kb, 231 Kb, and 1.7 Mb. TDPs with prominent ~11 Kb TDs feature the conjoint loss of TP53 and BRCA1. TDPs with ~231 Kb and ~1.7 Mb TDs associate with CCNE1 pathway activation or CDK12 disruptions, in conjunction with TP53 mutations. We prove the driver role of TP53 and BRCA1 abrogation for TDP induction by generating short-span TDP mammary tumors in genetically modified mouse models harboring deleterious mutations in only these two genes. Lastly, heterogeneous combinations of mutations mediated by TDs are selected for and contribute to the oncogenic burden of TDP tumors.

genomics↗