A. van Oudenaarden

Frequency encoding regulates cell type composition in the small intestine.

Intestinal homeostasis requires tight regulation of stem cell maintenance and differentiation to absorptive and secretory cell types, two major intestinal lineages. Key signaling pathways have been identified, but how they balance cell type composition remains unclear. We uncovered oscillatory expression of the Notch-t...

Random mtDNA mutagenesis maps genotype-phenotype associations across metabolic contexts and lineages

Mitochondrial DNA (mtDNA) mutations cause inherited disease, accumulate with age, and recur in tumors, yet their effects remain unresolved because existing models interrogate one engineered allele at a time. We developed mtDIVE, a random C→T mutagenesis platform for pooled mitochondrial forward genetics in human epithe...

Oncogenic fusions induce an extensive cancer-restricted cryptic proteome in Ewing sarcoma

Maintenance of nucleosome organization through replication and transcription counteracts aberrant coalescence of active chromatin.

Nucleosomes with their associated modifications organize and regulate the genome. It is unclear how this is integrated with the requirement of replication and transcription to access the DNA template without jeopardizing chromatin function. Here, we reveal a unified requirement for the histone chaperone FACT in mediati...

A single-cell multi-omic atlas of the human pancreas reveals potential for cellular plasticity across development, health, and disease.

A single-cell multiomics atlas of the human pancreas is presented, profiling over four million cells and nuclei from 57 donors across fetal development, adult homeostasis, and type 2 diabetes.

Single-cell multi-omics defines H3K27me3 remodelling in intervertebral disc degeneration with implications for regenerative intervention

This study demonstrates that eliminating repressive histone marks, together with CRISPR-mediated gene transactivation, enhances TBXT gene expression in human NPCs derived from degenerated aged discs.

Single-Cell Inference of Structural States Of Ribosomes

SCISSOR (Single-Cell Inference of Structural States of Ribosomes), a strategy that infers global translation activity in individual cells from the differential protection of ribosomal RNA against nuclease digestion, is introduced, establishing a framework for studying global translation control at single-cell resolutio...