# Elucidating CHD in Down Syndrome with Cardiac Organoids and 3D Genome Architecture

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $385,799

## Abstract

PROJECT SUMMARY
Down syndrome (DS) or Trisomy 21 (T21) is a prevalent chromosomal defect worldwide, often associated with
multiple cardiovascular and hematological anomalies. Congenital heart disease (CHD), affecting up to 50% of
DS patients, is a leading cause of morbidity and mortality in infants. CHD is primarily caused by dysregulated
transcriptional pathways. Although the 3D spatial organization of the genome has emerged as a crucial
mechanism for regulating chromatin accessibility, its role in cell-to-cell variability and gene regulation within CHD
remains poorly understood. In Aim 1, we will utilize 3D-vascularized cardiac organoids (3D-vCOs) and multi-
omics approaches to elucidate the mechanisms of DS-associated cardiovascular complications. We will employ
single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) to analyze the
vascular network and cardiomyocyte (CM) characteristics, thereby establishing phenotypes of DS-CHDs. Our
study will specifically focus on analyzing the vascular network and cardiomyocyte (CM) characteristics to
establish phenotypes of Down syndrome-associated congenital heart defects (DS-CHDs). In Aim 2, we will
perform Dip-C (Diploid Chromosome Conformation Capture) at specific timepoints during 3D-vCO culture (Day
3, Day 6, and Day 16) using DS patients iPSC lines. We will analyze the inter-chromosomal interactions (ICIs)
and 3D architecture of the genome in 3D-vCOs, namely focusing on differences among the CMs, CFs, and ECs
between DS-CHD versus DS-nonCHD patients. We anticipate gaining new mechanistic insights into the
pathogenesis of DS-CHDs and facilitating the development of novel therapeutic strategies aimed at mitigating
and reversing cellular abnormalities in the diseased heart.

## Key facts

- **NIH application ID:** 10852469
- **Project number:** 3R01HL141371-06S2
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lei Stanley Qi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $385,799
- **Award type:** 3
- **Project period:** 2018-05-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852469

## Citation

> US National Institutes of Health, RePORTER application 10852469, Elucidating CHD in Down Syndrome with Cardiac Organoids and 3D Genome Architecture (3R01HL141371-06S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10852469. Licensed CC0.

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