HCA Data Explorer

Integrated multiomic characterization of congenital heart disease

Access Granted
Updated January 18, 2024

The heart, the first organ to develop, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of CHD patients survive into adulthood but often suffer premature death from heart failure (HF) and non-cardiac causes. To gain insight into poorly understood disease progression, we performed single nuclear RNA sequencing (snRNA-seq) and analyzed 157,273 nuclei from donors and CHD patients, including hypoplastic left heart syndrome (HLHS) and Tetralogy of Fallot (TOF), two common forms of cyanotic CHD lesions, as well as, dilated (DCM) and hypertrophic (HCM) cardiomyopathies. We observed CHD specific cell states in cardiomyocytes (CMs) which had evidence of insulin resistance and increased FOXO and CRIM1 expression. Cardiac fibroblasts (CFs) in HLHS had enrichment for a low HIPPO and high YAP cell state characteristic of activated CFs. Imaging Mass Cytometry (IMC) uncovered the spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD in agreement with CHD predilection to infection and cancer. Our comprehensive CHD phenotyping provides a roadmap for future personalized medicine in CHD.

James F MartinBaylor College of Medicinejfmartin@bcm.edu
Matthew C Hill1
Zachary A Kadow1
Hali Long1
Yuka Morikawa2
Thomas J Martin1
Emma J Birks3
Kenneth S Campbell3
Jeanne Nerbonne4
Kory Lavine4
Lalita Wadhwa1
Jun Wang5
Diwakar Turaga1
Iki Adachi1
James F Martin1
1Baylor College of Medicine
2Texas Heart Institute
3University of Kentucky
4Washington University School of Medicine
5University of Texas Health Science Center
Ida Zucchi

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/c9e83418-a9f0-4ed1-ab4f-56d9513417bf

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://singlecell.broadinstitute.org/single_cell/study/SCP1852/integrated-multiomic-characterization-of-congenital-heart-disease
INSDC Project Accessions:
SRP375872, SRP393509
GEO Series Accessions:INSDC Study Accessions:

Analysis Portals

None

Project Label

MultiomicCongenitalHeartDisease

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

2 anatomical entities

Organ Part

3 organ parts

Selected Cell Types

2 cell types

Disease Status (Specimen)

10 disease statuses

Disease Status (Donor)

23 disease statuses

Development Stage

4 development stages

Library Construction Method

3 library construction methods

Nucleic Acid Source

2 nucleic acid sources

Paired End

false, true

Analysis Protocol

ATAC_tracks, processed_matrix_generation, raw_matrix_generation, umap_generation

File Format

9 file formats

Cell Count Estimate

157.3k

Donor Count

33
bigWig24 file(s)csv1 file(s)csv.gz16 file(s)fastq.gz134 file(s)mtx.gz4 file(s)tsv.gz6 file(s)txt1 file(s)txt.gz2 file(s)xlsx1 file(s)