# A Cellular Resolution Census of the Developing Human Brain

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $1,390,737

## Abstract

Project Summary/Abstract
We aim to create a spatiotemporal single cell resolution map of the developing human neocortex in order to
establish how many distinct cell types are present and to unravel their complex developmental history. We will
build our analysis on a multimodal classification of cells types based on transcriptomic signatures but
complemented where possible by physiological and epigenetic features. We will also examine transient cell
populations present only during developmental stages, and we will retain positional information for all our cell
data to create a developmental cell atlas that plots the diversity of cell types according to their locations in the
growing human brain. We have developed innovative strategies for massively parallel profiling of molecular
and physiological properties of primary human cortical cells using droplet based capture technologies, high
content microscopy, and paired physiological responses to transcriptional state. We propose to conduct our
integrated cellular survey of developing human brain in specific regions of the cortex, as well as in the striatum,
thalamus, hypothalamus and cerebellum, and we will use single nuclei sequencing to unlock developmental
time points that have been traditionally difficult to study. Our project will shed light on the origins of cellular
diversity in the human cortex by addressing three specific aims: 1) We will use single cell RNA-sequencing to
interrogate how neurogenesis and gliogenesis proceed and give rise to key cell types in the developed brain.
We hypothesize that key events promoting regionalization and connectivity can be transcriptionally
distinguished from the first trimester to postnatal stages, providing insights into how cell identity is determined.
2) Our developmental approach to the human brain cell atlas provides an opportunity to characterize transient
cell populations that appear early in development in the marginal zone and subplate regions, and disappear at
neonatal stages. These cell types are presumed to play important roles in establishing brain architecture and
function, but they remain poorly characterized in developing human brain. We hypothesize the heterogeneity of
these populations can be identified transcriptionally and can explain a diverse set of roles for these transient
populations. 3) Transcriptional states are a powerful tool for cell type identification, but they do not capture the
entire complexity of molecular features. We will profile cell-specific agonist responses and chromatin state that
reflect heterogeneity within defined transcriptional classes. We hypothesize that the intersection of
physiological state and epigenetic state to transcription will provide additional nuance to cell type classification.
Our results will provide a framework of cellular taxonomy in the developing human brain and create a
comprehensive cellular resolution map of molecularly defined cell types throughout functional regions of the
human brai...

## Key facts

- **NIH application ID:** 10165826
- **Project number:** 5U01MH114825-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Eric J Huang
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,390,737
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165826

## Citation

> US National Institutes of Health, RePORTER application 10165826, A Cellular Resolution Census of the Developing Human Brain (5U01MH114825-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10165826. Licensed CC0.

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