# The Spatiotemporal Landscape of the Human Brain Epitranscriptome

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $654,227

## Abstract

ABSTRACT
 The human Brainspan data was created to identify all transcripts involved in neural development and to
help understand of how specific risk genes affect human brain development. In addition, these data will have
important clinical relevance for translational medicine; these data can help discern which risk alleles associated
with psychiatric and neurological disorders influence transcription and alternative splicing across different
regions and developmental stages. Also, most Brainspan samples were processing for whole-genome
sequencing (WGS) and/or DNA methylation analysis, which enables direct comparisons of single basepair
changes, copy number variation, and RNA editing events in the developing human brain. As such, Brainspan
data holds biologically and clinically important data on the genetic and molecular mechanisms underlying the
development and increased disease susceptibility of the human brain.
 To expand upon this resource, we aim to create a matched profile of the human brains RNA
modification landscape (epitranscriptome), for both methyl-6-adenosine (m6A) and 5-methyl-cytosine (5mC).
We will profile the developmental trajectory of the RNA modifications and their activity in non-coding regions
and impact on splicing, RNA editing, AU-rich regulation of transcripts, and association with DNA methylation
changes (epigenetics). Finally, we will also test the impact of these modifications from patient-derived iPS cells
that will be grown and assayed over five time points. This will be accomplished over five years, and across
1,075 samples, across the Mason and Sestan labs, with collaborators at the Broad institute available to help
with assays and access to GTEx data from adult brains with m6A profiles.
 We will achieve these goals across three main aims. (1) Create a neuro-developmental map for
epitranscriptome sites and levels, with an emphasis on m6A and m5C, for 35 brains from four time periods, and
five regions of the brain, chosen based on their large differences seen in the BrainSpan data and prior
implication in neurological development. (2) Detail the inter-individual variation in epitranscriptome levels and
their epigenetic regulation using m6A variation with the changes in expression levels, and then link epigenetic
changes to altered gene expression and m6A regulation. (3) We will delineate the epitranscriptome changes in
autism brains and manifestation in patient-derived iPS cells, including an examination of epitranscriptome
variation across 30 banked Autistic brain samples and testing of the impact on disruption of the readers and
writers of RNA regulation (on induced pluripotent stem cells). These will represent the first-ever
epitranscriptome maps from primary tissue of Autism brains and help guide future studies that examine the
dysregulation of Autism gene expression networks and epitranscriptome states.

## Key facts

- **NIH application ID:** 10189699
- **Project number:** 5R01MH117406-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Christopher Edward Mason
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $654,227
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10189699

## Citation

> US National Institutes of Health, RePORTER application 10189699, The Spatiotemporal Landscape of the Human Brain Epitranscriptome (5R01MH117406-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10189699. Licensed CC0.

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