Publications by authors named "N Shapovalova"

-acting regulatory enhancer elements are valuable tools for gaining cell type-specific genetic access. Leveraging large chromatin accessibility atlases, putative enhancer sequences can be identified and deployed in adeno-associated virus (AAV) delivery platforms. However, a significant bottleneck in enhancer AAV discovery is charting their detailed expression patterns , a process that currently requires gold-standard one-by-one testing.

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The mammalian cortex is composed of a highly diverse set of cell types and develops through a series of temporally regulated events that build out the cell type and circuit foundation for cortical function. The mechanisms underlying the development of different cell types remain elusive. Single-cell transcriptomics provides the capacity to systematically study cell types across the entire temporal range of cortical development.

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Article Synopsis
  • Biological aging involves a gradual loss of homeostasis in molecular and cellular functions, particularly in the brain, which contains diverse cell types that differ in their aging resilience.
  • This study offers an extensive single-cell RNA sequencing dataset of approximately 1.2 million transcriptomes from brain cells in young and aged mice, identifying 847 cell clusters and 14 age-biased clusters predominantly involving glial types.
  • Key findings reveal specific gene expression changes with aging, including decreased neuronal function genes and increased immune-related genes, particularly in cells around the third ventricle of the hypothalamus, suggesting its critical role in the aging process of the mouse brain.
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Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies.

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We present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos.

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