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Resolving cellular and anatomical complexity of the brainstem using single-cell genomics

Award Number: R01MH138332
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/13/2026
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Resolving cellular and anatomical complexity of the brainstem using single-cell genomics - PROJECT SUMMARY The brain is an extraordinarily complex organ containing many millions of neurons and non-neuronal cells that are organized into highly specialized yet intricately integrated circuits controlling various activities, such as sensory perception, motor control, and cognitive processes. The brainstem is a critical region responsible for regulating essential bodily functions, like heart rate, blood pressure, and digestion, and thus maintaining body homeostasis. The individual neurons in brainstem can be classified into types based on shared characteristics like gene expression. Binning individual cells into cell types is fundamental for advancing our understanding of complex biological systems, like the brain, from normal tissue function to disease processes. The characterization of cell types enables creation of tools to gain genetic access to groups of cells, it enables dissection of cellular heterogeneity, identify key players in various contexts like disease and aging, and lay the groundwork for targeted interventions and therapies. We recently built a comprehensive, high-resolution atlas of cell types across the entire adult mouse brain and the cell type diversity in brainstem exceeded our expectations. Brainstem is home to a highly heterogeneous group of neurons that does not share a specific gene module, yet these neurons are highly similar to one another. In addition, these cell types intermingle in various regions and their function is strongly determined by their input/output relationship. This suggests that a high-dimensional combinatorial gene expression code is needed to resolve the unique transcriptomic cell types in this region. Our goal is to create a refined atlas of cell types in brainstem using a combination of single cell transcriptomic profiling, spatial transcriptomic profiling, and mapping of projection patterns to transcriptomic cell types in brainstem. In addition, we will computationally align brain stem cell types from mouse, non-human primate, and human to define a cross-species consensus atlas of brain stem. Cell type homologies across species can be established based on conserved marker expression. This enables inference of cellular properties, such as long- range projection targets, that are difficult to measure in humans. The proposed efforts will lead to a significantly improved understanding of brainstem cell types and their function and lay the foundation for a better understanding of disease processes related to that region.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $1,880,723 )
2026	2026	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Mental Health Research Grants	000	1	3/11/2026	NEW	$1,880,723
														Subtotal = $1,880,723

Grand Total All Awards = $1,880,723

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Resolving cellular and anatomical complexity of the brainstem using single-cell genomics

Award Number: R01MH138332

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/13/2026

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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