A5042851935- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Multiple Sclerosis Research Studies
- Nuclear Receptors and Signaling
- Wnt/β-catenin signaling in development and cancer
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Immune cells in cancer
- Cancer-related gene regulation
- Gene Regulatory Network Analysis
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Extracellular vesicles in disease
- Zebrafish Biomedical Research Applications
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- RNA regulation and disease
- RNA Interference and Gene Delivery
- Congenital heart defects research
Karolinska Institutet
2016-2025
Star Technology and Research (United States)
2024
Yale University
2021
Broad Institute
2021
Laboratory of Molecular Genetics
2008-2019
Ming Wai Lau Centre for Reparative Medicine
2019
Science for Life Laboratory
2017
The Gurdon Institute
2010-2014
University of Cambridge
2010-2014
Wellcome Trust
2010
The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major types cortex. identified numerous marker genes,...
Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of oligodendrocyte lineage from 10 regions mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 which represent continuum Pdgfra(+) precursor (OPCs) to mature oligodendrocytes. Initial stages differentiation similar across CNS, whereas subsets oligodendrocytes enriched specific brain. Newly formed...
Sensory functions of the vagus nerve are critical for conscious perceptions and monitoring visceral in cardio-pulmonary gastrointestinal systems. Here, we present a comprehensive identification, classification, validation neuron types neural crest (jugular) placode (nodose) derived vagal ganglia by single-cell RNA sequencing (scRNA-seq) transcriptomic analysis. Our results reveal major differences between neurons from different embryonic origins. Jugular exhibit fundamental similarities to...
Pdgfra+ oligodendrocyte precursor cells (OPCs) arise in distinct specification waves during embryogenesis the central nervous system (CNS). It is unclear whether there a correlation between these and different (OL) states at adult stages. Here, we present bulk single-cell transcriptomics resources providing insights on how transitions occur. We found that post-natal OPCs from brain spinal cord similar transcriptional signatures. Moreover, OPC progeny of E13.5 electrophysiological profiles to...
Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells context
Spatial omics emerged as a new frontier of biological and biomedical research. Here, we present spatial-CUT&Tag for spatially resolved genome-wide profiling histone modifications by combining in situ CUT&Tag chemistry, microfluidic deterministic barcoding, next-generation sequencing. Spatially chromatin states mouse embryos revealed tissue-type-specific epigenetic regulations concordance with ENCODE references provide spatial information at tissue scale. Spatial-CUT&Tag control the cortical...
Abstract Emerging spatial technologies, including transcriptomics and epigenomics, are becoming powerful tools for profiling of cellular states in the tissue context 1–5 . However, current methods capture only one layer omics information at a time, precluding possibility examining mechanistic relationship across central dogma molecular biology. Here, we present two technologies spatially resolved, genome-wide, joint epigenome transcriptome by cosequencing chromatin accessibility gene...
The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1-3. Methods based on conformation capture have mapped structures in neuronal systems such as vitro differentiated neurons, neurons isolated through fluorescence-activated sorting from cortical tissues pooled different animals dissociated whole hippocampi4-6. However, changes organization captured by imaging, the relocation Bdnf away nuclear periphery after activation7, are...
Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single-cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the dynamics of modeling temporal regional rates progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing spatial expression profiling using situ sequencing (ISS), we annotated neighborhoods found...
Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer's disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant oligodendrocytes (OLs). By cell-type-specific deletion Bace1 a humanized knock-in AD model, APP
The Wnts are a family of glycoproteins that regulate cell proliferation, fate decisions, and differentiation. In our study, we examined the contribution to development ventral midbrain (VM) dopaminergic (DA) neurons. Our results show β-catenin is expressed in DA precursor cells signaling takes place these cells, as assessed TOPGAL [Tcf optimal-promoter β-galactosidase] reporter mice. We also found Wnt-1, -3a, -5a expression differentially regulated during partially purified distinctively VM...
Dopamine (DA) cell replacement therapy in Parkinson disease (PD) can be achieved using human fetal mesencephalic tissue; however, limited tissue availability has hindered further developments. Embryonic stem cells provide a promising alternative, but poor survival and risk of teratoma formation have prevented their clinical application. We present here method for generating large numbers DA neurons based on expanding differentiating ventral midbrain (VM) neural cells/progenitors the presence...
Induced pluripotency requires the expression of defined factors and culture conditions that support self-renewal embryonic stem (ES) cells [1Takahashi K. Yamanaka S. Induction pluripotent from mouse adult fibroblast cultures by factors.Cell. 2006; 126: 663-676Abstract Full Text PDF PubMed Scopus (18861) Google Scholar]. Small molecule inhibition MAP kinase (MEK) glycogen synthase 3 (GSK3) with LIF (2i/LIF) provides an optimal environment for ES [2Ying Q.L. Wray J. Nichols Batlle-Morera L....
Abstract Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with local environment or their interactions different neuron types. Here, we that distinct populations have spatial preference in mammalian central nervous system (CNS). We found type 2 (MOL2) is enriched spinal cord when compared to brain, while types 5 and 6 (MOL5/6) increase contribution OL lineage age all analyzed regions. MOL2...
Abstract Mammalian genomes encode tens of thousands noncoding RNAs. Most transcripts exhibit nuclear localization and several have been shown to play a role in the regulation gene expression chromatin remodeling. To investigate function such RNAs, methods massively map genomic interacting sites multiple developed; however, these some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated sequenced (RADICL-seq), technology that maps genome-wide RNA–chromatin interactions...
Abstract Probing histone modifications at a single-cell level in thousands of cells has been enabled by technologies such as CUT&Tag. Here we describe nano-CUT&Tag (nano-CT), which allows simultaneous mapping up to three epigenomic modalities resolution using nanobody-Tn5 fusion proteins. Multimodal nano-CT is compatible with starting materials low 25,000–200,000 and significantly higher sensitivity number fragments per cell than We use simultaneously profile chromatin accessibility,...
Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG) and myelin immune cells, which are thought to be the main drivers of MS susceptibility. We found that genes exhibit primed chromatin state in single mouse human OLG non-disease context, compatible with transitions immune-competent states MS. identified BACH1 STAT1 as transcription factors involved gene regulation oligodendrocyte precursor cells (OPCs). A subset presents bivalency H3K4me3/H3K27me3 OPCs,...