Biology subjects

Parmaksiz, D.

Publications and source records attributed to Parmaksiz, D..

4 recordsLinked to original sources

bioRxiv2026

Neuronal and vascular genome-maintenance states organize opposing multicellular architectures in the aging brain

Genome maintenance is usually treated as cell-intrinsic, yet brain cells age within multicellular neighborhoods. Whether a cell's DNA damage response (DDR) state is systematically embedded in native tissue architecture is unknown. We used MERFISH to map curated repair programs across 604,252 cells in matched sections from 2-3 and 22-month-old mice. Regional DDR expression and coordination formed an age-dependent mosaic, accompanied by immune and oligodendroglial shifts. Independent metacell and distance-resolved analyses identified a consistent anchor-dependent organization. Low-DDR neurons occupied immune- and OPC-oligodendroglial-rich niches. In contrast, DDR-high vascular anchors were associated with vascular-cell enrichment and, in cortex and cerebral nuclei, OPC-oligodendroglial enrichment, whereas immune cells were enriched around DDR-low vascular anchors. Thus, genome-maintenance state was associated with distinct anchor-cell-specific spatial context depending on anchor-cell identity and its DDR transcriptional state. These opposing neuronal and vascular patterns define anchor-dependent genome-maintenance niches as a spatial feature of brain aging, with implications for regional vulnerability.

neuroscience↗

bioRxiv2026

Scale-Aware Compositional Inference Improves Reproducibility and Uncovers Convergent Aging Programs in Spatial Transcriptomics

Spatial transcriptomics enables analysis of molecular organization with anatomical context. Existing spatial differential expression methods are restricted to within-sample inference, forcing between-sample comparisons to rely on approaches adapted from single-cell RNA-seq. Here, we establish a scale-aware inference framework for spatial differential expression by modeling compositional constraints and variation in total RNA abundance rather than removing them through normalization, enabling calibrated between-sample inference at cell-level resolution. Our method produces more reliable results in simulated data and different spatial platforms. When applied to aged mouse brains, the analysis reveals converging aging-associated programs involving cellular signaling, membrane homeostasis, and neurovasculature across independent datasets.

genomics↗

bioRxiv2024

Brain-wide connectivity and novelty response of the dorsal endopiriform nucleus in mice

The dorsal endopiriform nucleus (EPd) is an enigmatic cortical subplate structure located inside the piriform cortex that shares a similar developmental origin with the claustrum. Although the EPd has been previously implicated in epilepsy and olfactory processing, its anatomical organization, connectivity patterns, and function remain largely unclear due to a lack of specific molecular markers. Our previous mapping study serendipitously identified that the Oxt receptor (Oxtr) is densely expressed in the EPd. Subsequent immunohistochemical and spatial transcriptomic analyses confirmed that Oxtr expression is enriched in the EPd, revealing distinct molecular organization compared to the neighboring claustrum. Whole brain input-output mapping of EPd Oxtr-positive neurons unveils extensive bidirectional connections to the ventral half of the brain, orchestrating functional circuits regulating olfaction, internal state, and emotion. Furthermore, our in-vivo miniscope recordings show that EPd Oxtr neurons exhibit high baseline activity during exploratory behavior, with a sharp decrease in activity in response to novel stimuli. This suggests that the EPd regulates interoceptive states and likely plays a role in adapting to novel exteroceptive cues.

neuroscience↗

bioRxiv2023

epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains

During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in {gamma}-aminobutyric acid-producing (GABAergic), cortical layer-specific cell types, and microglia as key players in shaping early postnatal brain development. We find contrasting changes in GABAergic neuronal densities between cortical and striatal areas, stabilizing at P12. Moreover, somatostatin-expressing cortical interneurons undergo regionally distinct density reductions, while vasoactive intestinal peptide-expressing interneurons show no significant changes. Remarkably, microglia transition from high density in white matter tracks to gray matter at P10, and show selective density increases in sensory processing areas that correlate with the emergence of individual sensory modalities. Lastly, we create an open-access web-visualization (https://kimlab.io/brain-map/epDevAtlas) for cell-type growth charts and developmental atlases for all postnatal time points.

neuroscience↗