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Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues.
Nat Methods
January 2025
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often limited to one or two modalities, offering an incomplete view of cellular identity. Here we present spatial-Mux-seq, a multimodal spatial technology that allows simultaneous profiling of five different modalities: two histone modifications, chromatin accessibility, whole transcriptome and a panel of proteins at tissue scale and cellular level in a spatially resolved manner.
View Article and Find Full Text PDFCoordinated neuron-glia regeneration through Notch signaling in planarians.
PLoS Genet
January 2025
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Some animals can regenerate large missing regions of their nervous system, requiring mechanisms to restore the pattern, numbers, and wiring of diverse neuron classes. Because injuries are unpredictable, regeneration must be accomplished from an unlimited number of starting points. Coordinated regeneration of neuron-glia architecture is thus a major challenge and remains poorly understood.
View Article and Find Full Text PDF"Energetics of the outer retina II: Calculation of a spatio-temporal energy budget in retinal pigment epithelium and photoreceptor cells based on quantification of cellular processes".
PLoS One
January 2025
UCL Institute of Ophthalmology, University College London, London, United Kingdom.
The outer retina (OR) is highly energy demanding. Impaired energy metabolism combined with high demands are expected to cause energy insufficiencies that make the OR susceptible to complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used to calculate the ATP expenditure of the main energy-consuming processes in three cell types of the OR for the night and two different periods during the day.
View Article and Find Full Text PDFDiverse sources of inhibition serve to modulate circuits and control cell assembly spiking across various timescales. For example, in hippocampus area CA1 the competition between inhibition and excitation organizes spike timing of pyramidal cells (PYR) in network events, including sharp wave-ripples (SPW-R). Specific cellular-synaptic sources of inhibition in SPW-R remain unclear, as there are >20 types of GABAergic interneurons in CA1.
View Article and Find Full Text PDFBackground: Deficiency in the lysosomal enzyme, glucocerebrosidase (GCase), caused by mutations in the GBA1 gene, is the most common genetic risk factor for Parkinson's disease (PD). However, the consequence of reduced enzyme activity within neural cell sub-types remains ambiguous. Thus, the purpose of this study was to define the effect of GCase deficiency specifically in human astrocytes and test their non-cell autonomous influence upon dopaminergic neurons in a midbrain organoid model of PD.
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