Biology subjects

Kapen, I.

Publications and source records attributed to Kapen, I..

6 recordsLinked to original sources

bioRxiv2026

MapMyCells: High-performance mapping of unlabeled cell-by-gene data to reference brain taxonomies

Single-cell mapping methods convert raw, heterogeneous single-cell datasets into interpretable and comparable representations of biological identity. As reference cell-type taxonomies mature, mapping new datasets to shared references has become a central strategy for enabling cross-study integration, reproducible annotation, and cumulative biological knowledge. Here we present MapMyCells, an open-source framework designed to align diverse single-cell omics datasets to hierarchical reference taxonomies with minimal preprocessing. MapMyCells provides out-of-the-box support for an expanding set of high-quality brain cell-type references generated by the Allen Institute for Brain Science, the BRAIN Initiative, and the Seattle Alzheimers Disease Brain Cell Atlas, including whole-brain mouse and human atlases, aging and Alzheimers disease cohorts, and a cross-species consensus taxonomy initially focused on the basal ganglia. MapMyCells enables efficient mapping of hundreds of thousands of cells on standard workstations without specialized hardware, providing a deterministic, scalable, and modality-agnostic approach that is robust across species and molecular assays. The framework produces interpretable confidence metrics and quantitative summaries of mapping performance, allowing users to evaluate assignment precision and accuracy. We demonstrate the mapping of unlabeled transcriptomic, epigenomic, and spatial datasets to reference taxonomies and describe a general workflow for preparing arbitrary hierarchical taxonomies for reference-based mapping. As the ecosystem of single-cell reference atlases expands, MapMyCells offers a practical and reproducible solution for community-scale cell-type annotation and cross-dataset integration, supporting the development of unified and extensible brain cell atlases.

bioinformatics↗

bioRxiv2026

Morphoelectric Diversity and Specialization of Neuronal Cell Types in the Primate Striatum

The basal ganglia are evolutionary ancient subcortical nuclei that form interconnected loops with the neocortex and limbic system to regulate movement, learning, habit formation, emotion, and motivation. Their dysfunction contributes to major neurological and psychiatric disorders, yet most cellular-level insights derive from rodent studies, leaving knowledge gaps in humans and translationally relevant primate species. To address this, we generated multi-modal Patch-seq data linking transcriptomic identity with morphological and electrophysiological properties in macaque striatum, the input nucleus of the basal ganglia. We found underappreciated diversity among medium spiny neurons, including non-canonical types, and variation aligned with functional gradients. Interneurons also exhibited spatial variation and even greater morphoelectric diversity, highlighting their functional modularity. Despite broad evolutionary conservation, we identified primate-specific features and key differences from rodent striatal neurons. By integrating molecular classification with cellular properties that shape network function, our findings provide insights into the functional organization of the primate striatum.

neuroscience↗

bioRxiv2026

A consensus spinal cord cell type atlas across mouse, macaque, and human

The spinal cord contains evolutionarily conserved cell types critical for motor function, sensory processing, and autonomic regulation, many of which are implicated in diverse neurological diseases and injuries. Yet the field lacks a comprehensive molecular characterization of cellular diversity in human, macaque, and mouse spinal cord. Here, we present a unified, cross-species cell type atlas based on the integration of single-nucleus gene expression, chromatin accessibility, and spatial transcriptomic data from segments within cervical, thoracic, lumbar, and sacral regions, including motor neurons (MNs) sampled across the entire rostro-caudal axis of the macaque spinal cord. Leveraging the spatial distributions of our molecularly defined cell types, we generated a cell type-guided anatomical map of spinal cord laminae and nuclei. We identified both conserved and species-specific cellular features, including gene expression patterns across distinct MN subtypes in the primate spinal cord. Cross-species cis-regulatory analysis and deep learning sequence models dissected the enhancer logic underlying viral targeting, uncovering conserved transcription factor grammar encoding cellular identity. Together, these results establish a unifying molecular and anatomical taxonomy of spinal cord cell types across species.

neuroscience↗

bioRxiv2025

Circuit specific specialization of human basal ganglia astrocytes

Astrocytes shape synapses and circuits, yet human basal ganglia astrocyte diversity is incompletely defined. We built a multimodal atlas by integrating single-nucleus RNA-sequencing and chromatin accessibility with DNA methylation, 3D chromatin conformation, and spatial transcriptomics, then mapped basal ganglia programs onto a whole-brain reference. Astrocytes segregated into three anatomical subgroups spanning striatal gray matter, extra-striatal gray matter, and white matter, with subgroup-biased neurotransmitter transporters and synapse-associated programs consistent with differences in dominant afferent input. Within striatum, dorsal and ventral astrocyte populations aligned with distinct microcircuits and were conserved in nonhuman primates. A deep learning sequence model identified subgroup-associated enhancer code and, when benchmarked against published enhancer-AAV datasets, supported the design of candidate viral tools to target basal ganglia astrocyte programs in vivo. Together, these data define major axes of human astrocyte specialization and provide a framework for cell type-specific dissection of basal ganglia function.

neuroscience↗

bioRxiv2025

Cross-species consensus atlas of the primate basal ganglia

The basal ganglia (BG) are conserved brain regions essential for motor control, learning, emotion, and cognition, and are implicated in neurological and psychiatric disease. Yet a unified cross-species taxonomy of BG cell types is lacking, limiting translation of BG circuit mechanisms, interpretation of human genetic risk, and development of cell type-targeted tools. We present a multiomic consensus atlas of 1.8 million nuclei from human, macaque, and marmoset spanning eight BG structures. Integrating cross-species gene expression, open chromatin, and spatial profiling enables definition of conserved and divergent cell types. Alignment to existing mouse and human atlases identifies 61 homologous cell types conserved over 80 million years. We identify a STRd D2 StrioMat Hybrid medium spiny neuron (MSN) type with molecular, electrophysiological, and morphological features that clarify hybrid MSN identities. Comparative cis-regulatory analysis reveals conserved sequence grammars that encode cell identity and inform viral targeting strategies, providing a foundational resource for BG evolution, function, and disease.

neuroscience↗

bioRxiv2025

A cross-species spatial transcriptomic atlas of the human and non-human primate basal ganglia

The basal ganglia are interconnected subcortical nuclei with complex topographical organization that orchestrate goal-directed behaviors and are implicated in neurodegenerative movement disorders. We generated a cellular-resolution, spatial transcriptomic atlas of the basal ganglia in human, rhesus macaque, and common marmoset, sampling over one million cells in each species. By integrating spatial data with a cross-species, consensus snRNA-seq cell type taxonomy, this atlas reveals conserved principles of molecular organization within and across structures. The cellular architecture is complex but highly stereotyped, with gene expression gradients superimposed onto discrete compartments. Extensive spatial sampling illuminates 3D gradients of molecular organization in the striatum and reveals cell type-specific core and shell compartments in the primate internal globus pallidus, which is conserved with mouse. This unified, cross-species spatial transcriptomic atlas will be a foundational resource for characterizing the molecular and functional organization of the basal ganglia and their roles in health and disease.

neuroscience↗