# Multimodal profiling of neurons in 3D human cortical organoids using patch-seq

> **NIH NIH R21** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2022 · $191,827

## Abstract

Abstract
Deficits in neurodevelopment and neuro-neuronal communications lead to mental disorders including autism
spectrum disorder and schizophrenia in humans. The progress in understanding the pathophysiology of mental
disorders is hampered by the lack of an integrative understanding of molecular, morphological and functional
properties of diverse cell types in human brain. While 3D cortical organoids derived from human induced
pluripotent stem cell (hiPSC) have been used to model neuropathology associated with virus infections and
neuropsychiatric disorders, it is still unclear whether the early brain developmental process can be faithfully
recapitulated by hiPSCs-based cortical organoids. Single-cell RNA sequencing of tens of thousands of cells of
human cortical organoids has provided an unprecedented opportunity to dissect the spatial and temporal
mechanism in early neuronal development in a cell type-specific manner. Such an approach has enabled the
classification of many neural types in several species and organoids based on transcriptomic profiles, which are
remarkably similar to the cellular compositions in human early brain development. Despite the advances in single
cell transcriptomics, the electrophysiological properties as well as morphological features of different types of
human neurons in brain organoids remain elusive. The labor-intensive nature of classical patch clamp
electrophysiology and the technical difficulties in recording from a heterogeneous population of neurons at
different stages of maturation had limited the abundance of functional data in human neurons. Because
electrophysiological phenotypes, contributed by morphological features, are governed by distinct membrane ion
channels and receptors, we hypothesize that electrophysiological (and possibly morphological) features of
human neurons can be predicted by single cell transcriptomic profiles. The primary goal of this exploratory project
is to establish a cell-census map based on electrophysiological, morphological and single cell transcriptomic
profiles in a hiPSC-3D cortical organoid model and to develop a transcriptomic algorithm for predicting cell
morphology-electrophysiology of human neurons. To achieve this goal, we propose: 1) to build a cell census
map of neural subtypes of human 3D cortical organoids with functional annotation at single cell resolution; 2) to
use using single cell transcriptomic profiles to predict the morphological and functional properties of cell types in
human 3D cortical organoids. This exploratory project will allow us to develop a database to integrate single cell
transcriptomes with cellular properties including electrophysiology and morphology profiles which enable
predictions of neuronal functions in brain development, health and disease based on transcriptomic data. This
study has enormous potential to enable future studies to ascertain the functional properties of neurons in
organoids based on transcriptomic data, thus facilit...

## Key facts

- **NIH application ID:** 10434140
- **Project number:** 5R21MH126420-02
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Wei Vivian Li
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $191,827
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434140

## Citation

> US National Institutes of Health, RePORTER application 10434140, Multimodal profiling of neurons in 3D human cortical organoids using patch-seq (5R21MH126420-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10434140. Licensed CC0.

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