Ed S. Lein

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

On 495 human Patch-seq neurons, cell type means predicted electrophysiology better than neural networks on scGPT embeddings or gene panels; fusing scGPT embeddings with cell type labels predicted best.

Iterative co-creation of harmonized human and non-human primate cellular and structural ontologies and 3D common coordinate frameworks for the basal ganglia

The paper describes the iterative creation of harmonized ontologies and 3D frameworks for the basal ganglia across human and non-human primates to enable cross-species comparisons of cellular and molecular data.

Multiregional single-cell profiling reveals shared and specialized cellular vulnerability in Alzheimer's disease

This study uses single-nucleus RNA-seq, ATAC-seq, and Multiome to analyze Alzheimer's disease across multiple brain regions, revealing shared and region-specific cellular vulnerabilities.

Multimodal characterization of variation in neuronal types in the mouse basal ganglia

This study uses multimodal Patch-seq data to show that gene expression gradients in mouse basal ganglia neurons correlate with spatial location, physiology, and morphology.

scVIP: personalized modeling of single-cell transcriptomes for developmental and disease phenotypes

scVIP models single-cell transcriptomes to predict phenotypes and infer trajectories in development and disease.

A Multimodal Single-Cell Epigenomic and 3D Genome Atlas of the Human Basal Ganglia

This paper creates a multimodal single-cell atlas of the human basal ganglia, revealing epigenomic and 3D genome features across cell types and linking them to disease-associated genetic risk.

Cell- and state-specific plasticity of striatal glutamatergic synapses is critical to the expression of levodopa-induced dyskinesia

This study identifies GluN2B-containing NMDAR up-regulation in iSPNs as a key mechanism in LID, showing that targeting these receptors can reduce dyskinesia without affecting levodopa's motor benefits.

A layered standards framework for integrating single-cell and spatial omics data into brain cell atlases

This paper introduces a standards framework for integrating single-cell and spatial omics data into brain cell atlases, enabling interoperable and reusable knowledge-ready resources.

Technical and biological sources of noise confound multiplexed enhancer AAV screening

The paper presents a barcoded multiplex strategy to screen enhancer AAVs using single-cell RNA sequencing and taxonomy mapping, but finds significant technical and biological noise complicates accurate expression pattern analysis.

Cell type-selective AADC expression reduces motor deficits and dyskinesia in Parkinson's disease mouse models

This study shows that cell type-specific AADC expression in Parkinson's disease models reduces motor deficits and dyskinesia more effectively than broad targeting.

A Community Standard Multispecies Cell Atlas of the Basal Ganglia

The paper presents a cross-species, multimodal atlas of the basal ganglia using single-cell transcriptomics and integrates epigenomic and spatial genomic data to enable cross-species comparisons.

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

MapMyCells maps unlabeled single-cell datasets to reference brain taxonomies, enabling cross-study integration and reproducible cell-type annotation.

B-BIND: Biophysical Bayesian Inference forNeurodegenerative Dynamics

This paper introduces a Bayesian framework to infer continuous disease states from discrete pathological protein measurements in Alzheimer's Disease, using pseudotime to model progression.

A Cross-Species Enhancer-AAV Toolkit for Cell Type-Specific Targeting Across the Basal Ganglia

The paper develops a cross-species enhancer-AAV toolkit for targeting specific cell types in the basal ganglia across species, validated in mouse and macaque.

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

The paper analyzes multi-modal Patch-seq data from macaque striatum to reveal morphoelectric diversity and functional specialization of neuronal cell types, highlighting primate-specific features and differences from rodents.

Single-cell multiomic human brain atlas reveals regulatory drivers of cortical regionality

The paper uses multiomic single-cell and spatial data to identify gene regulatory networks and transcription factors driving cortical regionality in the human brain.

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

The paper creates a cross-species spinal cord cell type atlas integrating data from mouse, macaque, and human, identifying conserved and species-specific features.

Single-cell Multiome Analysis of Chromatin State and Transcriptome in the Human Basal Ganglia

This paper presents a single-cell multiome atlas of the human basal ganglia, linking chromatin states and transcriptomes to cell-type identity and disease-associated variants.

An Integrated Single-Cell and Epigenomic Resource for Comparative Analysis of the Basal Ganglia

The paper presents an integrated single-cell and epigenomic resource for exploring basal ganglia datasets across species, enabling multi-omics and comparative analysis.

HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species

The paper examines HCN-channel properties in primate supragranular pyramidal neurons, finding conserved traits across species with some divergence in magnitude between humans and macaques.

The Caudate Nucleus Exhibits Distinct Pathology and Cell Type-Specific Responses Across Alzheimer's Disease

The paper maps AD-related pathological changes in the caudate nucleus at cellular resolution, identifying distinct features and cell type-specific responses.

Circuit specific specialization of human basal ganglia astrocytes

The paper defines major axes of human basal ganglia astrocyte specialization using a multimodal atlas and identifies enhancer code for targeted viral tools.

Cross-species consensus atlas of the primate basal ganglia

The paper creates a cross-species consensus atlas of primate basal ganglia cell types using multiomic data from human, macaque, and marmoset, identifying 61 conserved cell types and a novel hybrid medium spiny neuron type.

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

This paper creates a cross-species spatial transcriptomic atlas of the basal ganglia in human, rhesus macaque, and common marmoset, revealing conserved molecular organization and cell type-specific compartments.

Spatial patterning of transcriptional and regulatory programs in the primate subcortex

The paper presents a spatially resolved transcriptomic and gene regulatory atlas of primate subcortical regions, revealing spatially tuned transcriptional and regulatory programs across cell types.

A spatially-resolved human brain proteome atlas for understanding function and disease

The paper creates a spatially-resolved human brain proteome atlas, revealing protein diversity and functional specialization, and identifies therapeutic targets in epilepsy.

Evaluating Methods for the Prediction of Cell Type-Specific Enhancers in the Mammalian Cortex

The paper evaluates computational methods for predicting cell type-specific enhancers in the mouse cortex using in vivo validation data and finds that open chromatin and sequence models improve prediction accuracy.

Enhancer AAVs for targeting spinal motor neurons and descending motor pathways in rodents and macaque

The paper identifies enhancers for spinal motor neurons and develops AAV vectors to target these cells in rodents and macaques, enabling functional studies and potential therapeutic applications.

Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas Construction and Usage

This paper describes the construction and usage of the Human Reference Atlas (HRA) v2.0, which integrates multiscale data across 36 organs and provides tools for analysis and visualization.

AAV serotype PHP.eB achieves superior neuronal transduction efficiency compared to AAV9 in pigtail macaques following intracerebroventricular administration

This study compares AAV9 and AAV-PHP.eB transduction efficiency in pigtail macaques, finding AAV-PHP.eB achieves higher rates in cortical and spinal regions.