Biology subjects

Kroshilina, A.

Publications and source records attributed to Kroshilina, A..

3 recordsLinked to original sources

bioRxiv2024

Spatial Transcriptomic Analysis Identifies a SERPINA3-Expressing Astrocytic State Associated with the Human Neuritic Plaque Microenvironment

Single-nucleus transcriptomic studies have revealed glial cell states associated with Alzheimers disease; however, these nuclei are dissociated from the complex architecture of the human neocortex. Here, we successfully performed an unbiased distance-based analytic strategy on spatially-registered transcriptomic data. Leveraging immunohistochemistry in the same tissue section, our analyses prioritized SERPINA3 and other genes, such as metallothioneins, as altered in the vicinity of neuritic amyloid plaques. Results were validated at the protein level by immunofluorescence, highlighting that a reactive SERPINA3+ astrocyte subtype, Ast.5, plays a role in the plaque microenvironment.

neuroscience↗

bioRxiv2024

Relation of CMV and brain atrophy to trajectories of immunosenescence in diverse populations

Immunosenescence (ISC), the aging of the immune system, has largely been studied in populations of European descent. Here, circulating immune cell cytometric data from African-American, Hispanic, and non-Hispanic White participants were generated. Known and novel age effects were identified using either a meta-analysis approach or a parallel genetic approach. Most results are consistent across the three populations, but some cell populations display evidence of heterogeneity, such as a PD-L1+CD56+ NK cell subset. The study estimated "Immunological Age" (IA) during physiologic aging. While we found no relation of IA to Multiple Sclerosis, IA is associated with entorhinal cortex atrophy, a presymptomatic feature of Alzheimers disease, linking neurodegeneration and peripheral immunity. ISC trajectories were also inferred, highlighting age, CMV status, and genetic ancestry as key influences. Our assessment offers reference ISC trajectories for personalization of assessments of immune function over the life course in diverse populations.

immunology↗

bioRxiv2019

A Novel Tmem119-tdTomato Reporter Mouse Model for Studying Microglia in the Central Nervous System

Microglia are resident immune cells of the central nervous system (CNS). The exact role of microglia in the physiopathology of CNS disorders is not clear due to lack of tools to discriminate between CNS resident and infiltrated innate immune cells. Here, we present a novel reporter mouse model targeting a microglia-specific marker (TMEM119) for studying the function of microglia in health and disease. By placing a reporter cassette (GSG-3xFlag-P2A-tdTomato) between the coding sequence of exon 2 and 3UTR of the Tmem119 gene using CRISPR/Cas9 technology, we generated a Tmem119-tdTomato knock-in mouse strain. Gene expression assay showed no difference of endogenous Tmem119 mRNA level in the CNS of Tmem119tdTomato/+ relative to control Wild-type mice. The cells expressing tdTomato-were recognized by immunofluorescence staining using commercially available anti-TMEM119 antibodies. Using immunofluorescence and flow cytometry techniques, tdTomato+ cells were detected throughout the CNS, but not in peripheral tissues of adult Tmem119tdTomato/+ mice. In addition, aging does not seem to influence TMEM119 expression as tdTomato+ cells were detectable in the CNS of older mice (300 and 540 days old). Further immunofluorescence characterization shows that the tdTomato+ cells were highly colocalized with Iba1+ cells (microglia and macrophages) in the brain, but not with NeuN- (neurons), GFAP- (astrocytes) or Olig2- (oligodendrocytes) labeled cells. Moreover, flow cytometry analysis of brain tissues of adult mice demonstrates that the majority of microglial CD45lowCD11b+ cells (96.6%) are tdTomato positive. Functionally, using a laser-induced injury model, we measured time-lapse activation of tdTomato-labeled microglia by transcranial two-photon microscopy in live Tmem119tdTomato/+ mice. Taken together, the Tmem119-tdTomato reporter mouse model will serve as a valuable tool to specifically study the role of microglia in health and disease.

immunology↗