Publications by authors named "Kristen Vallejo"

Single-cell omics is advancing our understanding of selective neuronal vulnerability in Alzheimer's disease (AD), revealing specific subtypes that are either susceptible or resilient to neurodegeneration. Using single-nucleus and spatial transcriptomics to compare neocortical regions affected early (prefrontal cortex and precuneus) or late (primary visual cortex) in AD, we identified a resilient excitatory population in layer 4 of the primary visual cortex expressing , , and . Layer 4 neurons in association neocortex also remained relatively preserved as AD progressed and shared overlapping molecular signatures of resilience.

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Article Synopsis
  • - CSF1R-related disorder (CSF1R-RD) is a genetic neurodegenerative disease primarily affecting white matter due to mutations in the CSF1R gene, leading to a decline in brain function, particularly in an elderly man studied who showed symptoms of progressive dementia.
  • - Brain autopsy revealed features characteristic of adult-onset leukoencephalopathy (ALSP) associated with CSF1R-RD, and a novel genetic deletion in CSF1R was uncovered, which standard genetic tests hadn't detected.
  • - Further genomic analysis indicated two distinct states of microglia associated with the disease and showed that oligodendrocytes, critical for myelin formation, exhibited stress responses and failed to mature properly
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The cerebellum contains most of the neurons in the human brain and exhibits distinctive modes of development and aging. In this work, by developing our single-cell three-dimensional (3D) genome assay-diploid chromosome conformation capture, or Dip-C-into population-scale (Pop-C) and virus-enriched (vDip-C) modes, we resolved the first 3D genome structures of single cerebellar cells, created life-spanning 3D genome atlases for both humans and mice, and jointly measured transcriptome and chromatin accessibility during development. We found that although the transcriptome and chromatin accessibility of cerebellar granule neurons mature in early postnatal life, 3D genome architecture gradually remodels throughout life, establishing ultra-long-range intrachromosomal contacts and specific interchromosomal contacts that are rarely seen in neurons.

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The cerebellum contains most of the neurons in the human brain, and exhibits unique modes of development, malformation, and aging. For example, granule cells-the most abundant neuron type-develop unusually late and exhibit unique nuclear morphology. Here, by developing our high-resolution single-cell 3D genome assay Dip-C into population-scale (Pop-C) and virus-enriched (vDip-C) modes, we were able to resolve the first 3D genome structures of single cerebellar cells, create life-spanning 3D genome atlases for both human and mouse, and jointly measure transcriptome and chromatin accessibility during development.

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