# Chromatin remodeling factor CHD7 regulates cardiac and craniofacial lymphatic vessel development

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2024 · $737,809

## Abstract

Project Summary
The anterior second heart ﬁeld (SHF) cells are a population of late differentiating cardiovascular
progenitor cells that contribute to myocardial cells, smooth muscle cells, and endothelial cells in
the heart. It was not discovered until recently that these SHF progenitors can also contribute to
cardiac lymphatic endothelial cells (LECs) as well as the lymphatics of the craniofacial area in
mice. Lymphatics play essential roles in regulating interstitial fluid homeostasis and immune cell
modulation. It is unclear whether lymphatic defects can cause congenital cardiac and craniofacial
malformations. Mutation in CHD7, a gene encoding Chromodomain Helicase DNA Binding Protein
7 that functions as an ATP-dependent chromatin remodeler, cause craniofacial defects and
cardiovascular malformations. It has been reported that CHD7 plays a cell-autonomous role in
SHF progenitors to regulate downstream gene expression. Our preliminary data further
demonstrated that CHD7 is highly expressed in cardiac lymphatic progenitors and chd7 mutant
zebrafish show defects in lymphatics in the craniofacial areas, on the out flow tract and the heart
ventricle. We will test the hypothesis that CHD7 regulates gene expression and chromatin
accessibility in cardiac and craniofacial LECs derived from SHF progenitors. We propose two
independent aims to 1) perform confocal and live imaging and lineage tracing to analyze the chd7
mutant phenotypes and SHF contributions to craniofacial and cardiac LECs; 2) perform single
nuclei Multiomic amalysis, spatial transcriptomics and CUT&RUN to determine the molecular
mechanisms by which CHD7 regulates downstream gene expression and chromatin landscapes.
Our proposed experiments will reveal previously unappreciated roles of CHD7 in LECs derived
from SHF progenitors and help identify CHD7 downstream target genes that can be potential
therapeutic targets for patients with CHD and lymphatic malformations.

## Key facts

- **NIH application ID:** 11000101
- **Project number:** 1R01HL176018-01
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Ching-Ling E Lien
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $737,809
- **Award type:** 1
- **Project period:** 2024-07-25 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11000101

## Citation

> US National Institutes of Health, RePORTER application 11000101, Chromatin remodeling factor CHD7 regulates cardiac and craniofacial lymphatic vessel development (1R01HL176018-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11000101. Licensed CC0.

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