Unified molecular approach for spatial epigenome, transcriptome, and cell lineages Published: April, 2025 Abstract:
Spatial epigenomics and multiomics can provide fine-grained insights into cellular states but their widespread adoption is limited by the requirement for bespoke slides and capture chemistries for each data modality. Here, we present SPatial assay... Read more »
Menin-MLL1 complex cooperates with NF-Y to promote HCC survival Published: April, 2025 Abstract:
Abstract
Identification of new therapeutic targets in hepatocellular carcinoma (HCC) remains critical. Chromatin regulating complexes are frequently mutated or aberrantly expressed in HCC, suggesting dysregulation of chromatin environments is a k... Read more »
Spatial transcriptomic imaging of an intact organism using volumetric DNA microscopy Published: March, 2025 Abstract:
Lymphatic, nervous and tumor tissues exhibit complex physiology arising from three-dimensional interactions within genetically unique microenvironments. Here we develop a technology capable of volumetrically imaging transcriptomes, genotypes and m... Read more »
SIRT6 activator fucoidan extends healthspan and lifespan in aged wild-type mice Published: March, 2025 Abstract:
Abstract
SIRT6 is a protein deacylase, deacetylase, and mono-ADP-ribosylase (mADPr) regulating biological pathways important for longevity including DNA repair and silencing of LINE1 retrotransposons. SIRT6 knockout mice die by 30 days of age, wh... Read more »
Multi-step genomics on single cells and live cultures in sub-nanoliter capsules Published: March, 2025 Abstract:
Abstract
Single-cell genomics encompasses a set of methods whereby hundreds to millions of cells are individually subjected to multiplexed assays including sequencing DNA, chromatin accessibility or modification, RNA, or combinations thereof ... Read more »
Distinct molecular mechanisms of stress habituation in the mouse hippocampus Published: March, 2025 Abstract:
Chronic stress is a risk factor for neuropsychiatric disorders, making the ability to adapt to repeated stress a crucial determinant of mental health. On a molecular level, it remains unclear whether repeated exposure to stress is characterized by... Read more »
Combinatorial mapping of E3 ubiquitin ligases to their target substrates Published: February, 2025 Abstract:
Highlights
Developed a combinatorial assay to test E3-substrate interactions at scale
Identified known and unknown E3-substrate relationships across three screens
Assessment of in silico models points to scal... Read more »
Cells transit through a quiescent-like state to convert to neurons at high rates Published: November, 2024 Abstract:
While transcription factors (TFs) provide essential cues for directing and redirecting cell fate, TFs alone are insufficient to drive cells to adopt alternative fates. Rather, transcription factors rely on receptive cell states to induce novel ide... Read more »
Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements Published: September, 2024 Abstract:
CRISPR-based gene activation (CRISPRa) is a strategy for upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbat... Read more »
Precision and efficacy of RNA-guided DNA integration in high-expressing muscle loci Published: September, 2024 Abstract:
Gene replacement therapies primarily rely on adeno-associated virus (AAV) vectors for transgene expression. However, episomal expression can decline over time due to vector loss or epigenetic silencing. CRISPR-based integration methods offer promi... Read more »
Rhabdomyosarcoma fusion oncoprotein initially pioneers a neural signature in vivo Published: July, 2024 Abstract:
Fusion-positive rhabdomyosarcoma is an aggressive pediatric cancer molecularly characterized by arrested myogenesis. The defining genetic driver, PAX3::FOXO1, functions as a chimeric gain-of-function transcription factor. An incomplete understandi... Read more »
CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly Published: June, 2024 Abstract:
The SWI/SNF (or BAF) complex is an essential chromatin remodeler that regulates DNA accessibility at developmental genes and enhancers. SWI/SNF subunits are among the most frequently mutated genes in cancer and neurodevelopmental disorders. These ... Read more »
Clock-dependent chromatin accessibility rhythms regulate circadian transcription Published: May, 2024 Abstract:
Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made in understanding the regulatory role of clock proteins in circadian rhythms... Read more »
Cellular reprogramming in vivo initiated by SOX4 pioneer factor activity Published: February, 2024 Abstract:
Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting cell fate is silenced and the new cell fate is activated has not been investigated in animals. In cell culture, pioneer transcription factors media... Read more »
The ncBAF complex regulates transcription in AML through H3K27ac sensing by BRD9 Published: December, 2023 Abstract:
The non-canonical BAF complex (ncBAF) subunit BRD9 is essential for acute myeloid leukemia (AML) cell viability but has an unclear role in leukemogenesis. Because BRD9 is required for ncBAF complex assembly through its DUF3512 domain, precise brom... Read more »
High-capacity sample multiplexing for single cell chromatin accessibility profiling Published: December, 2023 Abstract:
Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a nove... Read more »
A fast and inexpensive plate-based NGS library preparation method for insect genomics Published: November, 2023 Abstract:
Entomological sampling and storage conditions often prioritise efficiency, practicality and conservation of morphological characteristics, and may therefore be suboptimal for DNA preservation. This practice can impact downstream molecular applicat... Read more »
Combined Analysis of mRNA Expression and Open Chromatin in Microglia Published: August, 2023 Abstract:
The advance of single-cell RNA-sequencing technologies in the past years has enabled unprecedented insights into the complexity and heterogeneity of microglial cell states in the homeostatic and diseased brain. This includes rather complex proteom... Read more »
Volumetric imaging of an intact organism by a distributed molecular network Published: August, 2023 Abstract:
Lymphatic, nervous, and tumoral tissues, among others, exhibit physiology that emerges from three-dimensional interactions between genetically unique cells. A technology capable of volumetrically imaging transcriptomes, genotypes, and morphologies... Read more »
Spatial epigenome-transcriptome co-profiling of mammalian tissues. Published: April, 2023 Abstract:
Emerging spatial technologies, including spatial transcriptomics and spatial epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context. However, current methods capture only one layer of omics information at a... Read more »
Physiological reprogramming in vivo mediated by Sox4 pioneer factoractivity Published: January, 2023 Abstract:
Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting cell fate is silenced and the new cell fate is activated has not been investigated in animals. In cell culture, pioneer transcription factors media... Read more »
Optimized single-nucleus transcriptional profiling by combinatorialindexing. Published: October, 2022 Abstract:
Single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) is a powerful method for recovering gene expression data from an exponentially scalable number of individual cells or nuclei. However, sci-RNA-seq is a complex protocol that has histo... Read more »
Spatial profiling of chromatin accessibility in mouse and human tissues Published: August, 2022 Abstract:
Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context1. The emergence of spatial transcriptomics has enabled genome-scale gene expression m... Read more »
