# Functionally guided adult whole brain cell atlas in human and NHP

> **NIH NIH UM1** · ALLEN INSTITUTE · 2024 · $17,255,818

## Abstract

Progress in treating brain disorders has been frustratingly slow, in large part due to the extraordinary complexity of the
human brain and its inaccessibility to study. Remarkable advances in technologies for studying individual cells, most
notably single cell genomics, have revolutionized the study of complex nervous tissues and have been used to map cellular
diversity across the entire mouse brain with cell types defined by their specific patterns of gene usage and gene regulatory
mechanisms. These highly scalable methods have been successfully applied to brain tissue from human and other species
and are ready to be applied to whole brains from humans and non-human primates. A major challenge with studying the
human brain is bridging fields and scales from functional MRI and macroscale connectomics to histological, cellular and
molecular analyses. Bridging these domains is essential to creating a transformative new cell atlas that will describe the
cellular and molecular underpinnings of the functional organization of the human brain. An important recent
development from single cell genomic analysis is that cell types can be aligned across species and are highly conserved
across mammals from mice to humans, although more similar in evolutionarily closer primates than in rodents. This finding
amplifies the value of primate species in helping to understand human brains and infer cellular properties that cannot be
measured in humans.
The current proposal brings together a unique team of world leaders to tackle the challenge of creating a new human and
non-human primate cell atlas linked to functional brain architecture. Single cell transcriptomic, epigenomic and spatial
transcriptomics will be used to classify and spatially map cell types across the entire human, macaque and marmoset
brain, sampling based on brain maps derived from structural and functional imaging. Function-localizing fMRI in macaques
will allow the direct analysis of cellular correlates of functional topography. Advances in spatial transcriptomics will allow
an unprecedented whole primate brain map of cell types. Unique access to macaque tissues for analysis of cellular
anatomy and physiology allows the characterization of molecularly-defined cell types in many brain regions. Similar
techniques will be applied to living neurosurgically-derived human brain tissues, coupled with enhancer-AAV based tools
to allow selective genetic labeling of cell types. Finally, profiling regions central to perception, behavior and mood across
many individuals and diverse mammals will link genetic, environmental and evolutionary factors to cellular variation.
The outcome of these efforts will produce a new reference classification for cell types across the whole human and NHP
brain, spatial maps of molecularly defined cell types, and phenotypic characterization of fundamental brain cell types. The
classification will align homologous cell types from mice, marmosets, macaques and humans, allowing i...

## Key facts

- **NIH application ID:** 10880498
- **Project number:** 5UM1MH130981-03
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Ed Lein
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $17,255,818
- **Award type:** 5
- **Project period:** 2022-08-22 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880498

## Citation

> US National Institutes of Health, RePORTER application 10880498, Functionally guided adult whole brain cell atlas in human and NHP (5UM1MH130981-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10880498. Licensed CC0.

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