# Cell Identity Determination In Human Brain: Somatic mutation and cell lineage

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $695,233

## Abstract

Somatic mutations, present in some but not all cells of the brain, are increasingly implicated in
neurological and psychiatric diseases. Somatic mutations that arise during the cell divisions of prenatal brain
development are inherited in clonal fashion and can cause neurodevelopmental diseases such as epilepsy and
intellectual disability, even when present at low levels of mosaicism. The previous funding period of this grant
developed new methods and algorithms to analyze somatic mutations in postmortem human brain, and
technologies to sequence the genomes of single neurons, and has shown that each neuron has a unique
genome, with hundreds of developmental mutations present at birth, and dozens more mutations being added
each year of life. During prenatal life, 2-3 mutations mark each cell division, so that mutations make in
principal a permanent record of each cell division. Integrating the analysis of DNA marks of cell lineage with
patterns of gene expression that identify the different neural types in human brain potentially now enables the
discovery of the first systematic picture of the pattern of cell divisions that generates the cells of the human
brain. In this project, we will apply our existing methods to provide several scientific discoveries not otherwise
attainable, providing tools of widespread utility to the genetics and neuroscience communities.
 Our three Specific Aims will be to 1) use simultaneous analysis of DNA mutations and RNA gene
expression to map the lineage of neural cell types in cerebral cortex; 2) map clonal patterns across the surface
of the human cerebral cortex to see how they relate to functional subdivisions of the cortex; and 3) focus on the
analysis of development of human temporal lobe, which is subject to many unique conditions like temporal lobe
epilepsy.
 These data provide three major discoveries which have all been major goals of neuroscience and which
are not presently obtainable by other means: 1) the first direct cell lineage data from the adult human brain, 2)
a preliminary lineage map connecting neuronal cell classes, and 3) unique insight into temporal lobe
development.

## Key facts

- **NIH application ID:** 10447173
- **Project number:** 5R01NS032457-24
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Christopher A. Walsh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $695,233
- **Award type:** 5
- **Project period:** 1994-12-16 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447173

## Citation

> US National Institutes of Health, RePORTER application 10447173, Cell Identity Determination In Human Brain: Somatic mutation and cell lineage (5R01NS032457-24). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10447173. Licensed CC0.

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