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ArchVelo: archetypal velocity modeling for single-cell multi-omic trajectories

Inferring cellular dynamics from static single-cell data remains a central challenge in genomics. We introduce ArchVelo, a computational framework for modeling gene regulation and inferring trajectories from paired single-cell chromatin accessibility …

Eosinophils drive intestinal remodelling and innate defence in reproduction

Mammalian reproduction requires substantial immune adaptations to safeguard reproductive success and to ultimately shape the evolutionary trajectories of a species. Systemic and placental immunity shift towards tolerance during pregnancy; however, …

Metadomain and metaloop genome interactions in mammalian T cells

Recent studies have advanced understanding of chromosomal organization and its role in gene regulation, yet most analyses focus on short-range interactions (

Predictive modeling of molecular activity underlying physical cell-cell interactions

Interactions between cells are central to tissue organization and function in health and disease. Labeling immune partnerships by sortagging intercellular contacts (LIPSTIC) quantitatively measures direct physical cell-cell interactions. Combined …

Temporal and context-dependent requirements for the transcription factor Foxp3 expression in regulatory T cells

Regulatory T (Treg) cells, expressing the transcription factor Foxp3, are obligatory gatekeepers of immune responsiveness, yet the mechanisms by which Foxp3 governs the Treg transcriptional network remain incompletely understood. Using a novel …

3D chromatin structures precede genome activation in Drosophila embryogenesis

3D chromatin structure is critical for the regulation of gene expression during development. Here we used Micro-C assays at 100-bp resolution to map genome organization in Drosophila melanogaster throughout the first half of embryogenesis. These …

Cathelicidin antimicrobial peptides mediate immune protection in marsupial neonates

Marsupial neonates are born with immature immune systems, making them vulnerable to pathogens. While neonates receive maternal protection, they can also independently combat pathogens, although the mechanisms remain unknown. Using the sugar glider …

Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2

We present GuideScan2 for memory-efficient, parallelizable construction of high-specificity CRISPR guide RNA (gRNA) databases and user-friendly design and analysis of individual gRNAs and gRNA libraries for targeting coding and non-coding regions in …

Terminal differentiation and persistence of effector regulatory T cells essential for preventing intestinal inflammation

Regulatory T (Treg) cells are a specialized CD4+ T cell lineage with essential anti-inflammatory functions. Analysis of Treg cell adaptations to non-lymphoid tissues that enable their specialized immunosuppressive and tissue-supportive functions …

Engineered extrachromosomal oncogene amplifications promote tumorigenesis

Focal gene amplifications are among the most common cancer-associated mutations but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal …