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Series GSE217828 Query DataSets for GSE217828
Status Public on Jan 11, 2024
Title YAP Drives Assembly of a Spatially Colocalized Cellular Triad Required for Heart Renewal
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary After myocardial infarction (MI), the heart fails to renew, and the cardiac microenvironment is irreversibly disrupted. Inactivation of the Hippo signaling pathway can rebuild the post ischemic microenvironment and improve cardiac function. We investigated spatially resolved cellular relationships of neonatal and adult renewal-competent hearts to gain insight into inefficient mammalian heart renewal. Spatial transcriptomics (ST) and single-cell sequencing of adult control hearts and hearts expressing YAP5SA, an active version of the Hippo signaling pathway effector YAP, which models heart renewal, revealed a conserved, renewal-competent cardiomyocyte (CM) population in control hearts and amplified in YAP5SA hearts. This CM population was also found in the wildtype, renewal competent neonatal heart after myocardial infarction, as well as the adult human heart. Cardiac fibroblasts (CFs), expressing complement C3, colocalized with these CMs. In YAP5SA hearts and neonatal hearts post-MI, macrophages (MPs) expressing complement receptor C3ar1 also colocalized, creating a pro-renewal niche composed of the CM, CF and MP triad. Both C3 and C3ar1 loss-of-function in YAP5SA hearts similarly suppressed heart renewal, indicating that C3-expressing CFs, C3ar1-expressing MPs, and complement system signaling play a direct role in heart renewal
Overall design Single cell RNA sequencing and spatial transcriptomics were performed to examine MCM control versus MCM YAP5SA adult murine hearts

Single nucleus RNA sequencing were performed to examine wild type control and C3-/- p2 neonatal murine hearts 3 days after sham or MI surgeries.
Contributor(s) Kim JH, Li RG, Li X, Martin JF
Citation(s) 38510108
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 HL127717 Hippo and Wnt Signaling in Cardiac Regeneration TEXAS HEART INSTITUTE James F Martin
R01 HL130804 Optical elastography for assessment of myocardial regeneration BAYLOR COLLEGE OF MEDICINE James F Martin
R01 HL118761 Pitx2 in atrial fibrillation BAYLOR COLLEGE OF MEDICINE James F Martin
AHA_903651 Elucidating the role of complement in cardiac renewal Texas Medical Center Rich Gang
AHA_903411 Hippo pathway in cardiac fibroblast regulates macrophage recruitment following injury Texas Medical Center Fansen Meng
Submission date Nov 11, 2022
Last update date May 29, 2024
Contact name Jong H Kim
Organization name Baylor College of Medicine
Street address One Baylor Plaza
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM6727274 MCM control mouse heart spatial RNA-seq
GSM6727275 MCM-YAP5SA mouse heart spatial RNA-seq
GSM6727276 Control-AAV mouse heart CD45-enriched scRNA-seq
BioProject PRJNA900621

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE217828_RAW.tar 809.5 Mb (http)(custom) TAR (of CSV, TIFF)
GSE217828_scRNA_integrated.meta_data.csv.gz 191.5 Kb (ftp)(http) CSV
GSE217828_scRNA_integrated.normalized_count.csv.gz 36.7 Mb (ftp)(http) CSV
GSE217828_scRNA_integrated.raw_count.csv.gz 34.8 Mb (ftp)(http) CSV
GSE217828_snRNA_metadata.csv.gz 3.8 Mb (ftp)(http) CSV
GSE217828_snRNA_norm_umi.csv.gz 818.2 Mb (ftp)(http) CSV
GSE217828_snRNA_raw_umi.csv.gz 93.9 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data provided as supplementary file

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